Plate  i. 


I. 

PALE  YELLOW. 

11. 
LIGHT  YELLOW, 

HI. 

YELLOW. 

IV. 

REDDISH  YELLOW. 

:-^'mm^ 

V. 

YELLOWISH  RED. 

^^^^^^^^^^^^^^^^^^^^^^^^^^^^ 

VI. 

RED. 

^^^^^1 

VII. 

BROWNISH  RED. 

I^HI^I 

VIII. 

REDDISH  BROWN. 

IX. 

BROWNISH  BLACK. 

Scale  of  Urinary   Colors,  according  to  Vogel. 


Clinical 
Examination  of  the  Urine 

AND 

Urinary  Diagnosis 

A  Clinical  Guide  for  the  Use  of  Practitioners  and 
Students  of  Medicine  and  Surgery 


J.    BERGEN   OGDEN,   M.D. 


INSTRUCTOR  IN  CHEMISTRY,  HARVARD  UNIVERSITY  MEDICAL  SCHOOL  ;  ASSISTANT  IN  CLINICAL 

PATHOLOGY,  BOSTON  CITY  HOSPITAL  ;    MEDICAL  CHEMIST  TO  THE  CARNEY  HOSPITAL; 

VISITING  CHEMIST  TO  THE  LONG  ISLAND  HOSPITAL,  BOSTON. 


ILLUSTRATED 


PHILADELPHIA   AND   LONDON 

Vv^.  B.  SAUNDERS   &    COMPANY 
1 90 1 


Copyright,  1900, 
By  W.  B.  SAUNDERS  &  COMPANY. 


PRESS  OF 
W.   B.  SAUNDERS    &    COMPANY. 


I  ;  -  - 


TO 

3£Dwar2)  Sticftncg  XUHooJ),  a./IR.,  /1B.2).» 

PROFESSOR    OF    CHEMISTRY,    HARVARD    UNIVERSITY    MEDICAL    SCHOOL, 

AS  A  SLIGHT  TOKEN  OF  HIGHEST  ESTEEM  AS 

A   TEACHER  AND   FRIEND, 

THIS  VOLUME 

IS  RESPECTFULLY  DEDICATED  BY 

THE  AUTHOR. 


PREFACE. 


The  design  of  this  work  is  to  present  in  as  concise  a 
manner  as  possible  the  chemistry  of  the  urine  and  its  rela- 
tion to  physiologic  processes  ;  the  most  approved  working 
methods,  both  qualitative  and  quantitative  ;  the  diagnosis 
of  diseases  and  disturbances  of  the  kidneys  and  urinary 
passages. 

Since  most  of  the  books  on  the  urine  at  the  present  time 
are  devoted  almost  exclusively  to  urinary  chemistry,  and 
since  a  knowledge  of  urinary  diagnosis  is  obtainable  only 
by  an  extended  search  through  various  works  on  medicine, 
surgery,  pathology,  and  chemistry,  I  have  long  felt  the  need 
of  a  treatise  which  takes  up  in  detail  the  subject  of  urinary 
diagnosis  and  the  application  of  information  furnished  by 
careful  chemic  and  microscopic  examination  of  the  urine. 

The  work  naturally  falls  into  two  parts. 

In  Part  I  chemic  and  microscopic  methods  are  described 
in  detail,  and  numerous  illustrations,  many  of  which  are 
original,  have  been  introduced,  thus  enabling  the  student 
and  practitioner  who  has  not  had  special  training  in  urinary 
analysis  to  obtain  accurate  results. 

In  Part  II  special  attention  has  been  paid  to  diagnosis, 
which  includes  our  present  knowledge  of  the  character  of 
the  urine,  the  diagnosis  and  differential  diagnosis  of  dis- 
turbances and  diseases  of  the  kidneys  and  urinary  passages, 
whether  they  be  local  or  general,  medical  or  surgical  ;  a 
brief  enumeration  of  the  prominent  clinical  symptoms  of 
each  disease  ;  and,  finally,  the  peculiarities  of  the  urine  in 
certain  general  diseases  of  the  body. 

My  chief  object,  therefore,  in  presenting  this  w'ork  is  to 
furnish  the  student  and  practitioner  with  a  more  complete 
clinical  guide  to  urinary  diagnosis  than  I  have  heretofore 
met  with  in  a  single  volume. 

No  attempt  has  been  made  to  incorporate  in  this  volume 
more  than  a  limited  number  of  references  to  the  literature 

9 


10  PREFACE. 

on  the  various  urinary  subjects  that  have  been  considered. 
Those  references  given  are,  for  the  most  part,  to  subjects 
that  are  still  under  discussion,  or  to  those  that  are  com- 
paratively new  to  medical  literature. 

Numerous  books  and  original  monographs  have  been 
consulted,  and  the  views  of  standard  authorities  have  been 
freely  quoted  in  this  work.  I  have  endeavored  in  all  cases 
to  give  full  credit  to  the  various  writers  throughout  the  text. 
If  in  any  instances  I  have  been  remiss,  I  take  this  oppor- 
tunity of  thanking  those  who  have  unwittingly  aided  me  by 
their  researches  and  writings. 

In  conclusion,  I  wish  to  express  my  sincerest  thanks  to 
Dr.  Edward  S.  Wood  for  the  many  valuable  suggestions 
he  has  given  me  in  the  production  of  this  volume. 

J.  Bergen  Ogden. 

July,  igoo. 


CONTENTS 


PAGE 

Introduction 17 

CHAPTER  I. 

Constituents  of  Normal  Urine 21 

Physical  Properties  of  Urine .  24 

CHAPTER.  II.  ,,-— "^v 

Organic  Constituents  of  Normal  Urine (_At-^ 

Urea 41 

Table  of  Approximate   Proportions  of  Urea  in  Urine,  for  Clinical 

Use ,^55"-: 

Uric  Acid 59- 

Xanthin  Bases      yi 

Nucleic  Acid 75 

AUantoin 76 

Kreatin  and  Kreatinin 78 

The  Aromatic  Substances  in  Urine 80 

Urinary  Coloring-matters 90 

Other  Organic  Constituents  of  the  Urine 96 

CHAPTER  III. 

Inorganic  Constituents  of  Normal  Urine 99 

Chlorides 9^ 

■  Phosphates 'v|o^^- 

Sulphates      in 

Carbonates 115 

Iron  .    .                      116 

Hydrogen  Peroxide 1 16 

CHAPTER  IV. 

Abnormal  Constituents  of  Urine 117 

Proteids 117 

Albumin 118 

Globulin        122 

Albumoses 134 

Peptone 136 

Method  of  Separation  and  Identification  of  Proteids      139 

Nucleo-albumin 140 

Hemoglobin 142 

Fibrin 143 

CHAPTER  V. 

Carbohydrates     .       145 

Glucose 145 

Lactose 164 

11 


12  CONTENTS. 

PAGE 

Levulose 165 

Laiose                            166 

Substances  Allied  to  Sugar 167 

Inosite       .                 167 

Glycuronic  Acid 169 

Cane  Sugar 170 

Acetone             171 

Diacetic  Acid 174 

Bile 175 

Biliary  Acids 178 

Ehrlich's  Diazo  Reaction        182 

Various  Metallic  Substances      184 

Hematoporphyrin 187 

Melanin 190 

Ptomaines  and  Leucomaines. — Toxicity  of  Urine 191 

CHAPTER  VI. 

Urinary  Sediments 199 

Methods  of  Obtaining  Urinary  Sediments 200 

The  Preparation  of  Sediments  for  Microscopic  Examination      .    .    .  206 

Urinary  Sediments 207 

Nonorganized  Sediments         208 

Organized  Sediments 230 

Extraneous  Substances  Found  in  Urine 261 

Preservation  of  Urinary  Sediments 261 

Micro-organisms 263 

Parasites 267 

CHAPTER  Vn. 

Urinary  Concretions 270 


PART  11. 

Diagnosis 282 

CHAPTER  Vni. 

Disturbances  and  Diseases  of  the  Kidneys 282 

Active  Hyperemia 282 

Passive  Hyperemia 289 

Acute  Diffuse  Nephritis 292 

Subacute  Glomerular  Nephritis      300 

Chronic  Interstitial  Nephritis 305 

Senile  Interstitial  Nephritis 313 

Chronic  Diffuse  Nephritis 314 

Amyloid  Infiltration 317 

CHAPTER  IX. 

Diseases  of  the  Kidneys  (Continued) 321 

Tuberculosis  of  the  Kidneys 321 

Renal  Calculus 324 

Abscess  of  the  Kidney 326 

Renal  Embolism       327 

Tumors  of  the  Kidney 328 

Cystic  Disease  of  the  Kidneys 329 


CONTENTS.  13 

CHAPTER  X. 

PAGE 
DlSE.\SES     OF    THE    URINARY    TRACT    BELOW    THE     KiDNEY    PROPER  .      33 1 

Pyelitis      33^ 

Acute  Pyelitis 33^ 

Chronic  Pyelitis 333 

Calculous  Pyelitis 335 

Hydronephrosis 337 

Pyonephrosis 339 

Ureteritis 34^ 

Cystitis      342 

Acute  Cystitis 342 

Chronic  Cystitis 344 

Tuberculosis  of  the  Bladder 34^ 

Tumors  of  the  Bladder 34^ 

Prostatitis      35' 

Acute  Prostatitis 35' 

Prostatic  Abscess      ...        353 

Chronic  Prostatitis 353 

Tubercular  Prostatitis      35^ 

Cancer  of  the  Prostate ■- 357 

Urethritis      357 

Chyluria " 3^0 

Hemoglobinuria 3"2 

Pneumaturia , 3"4 

Uremia      3"5 

Diabetes  Mellitus 3^8 

Diabetic  Coma 373 

Diabetes  Insipidus 375 

CHAPTER  XI. 

The  Urine  in  Diseases  outside  of  the  Urinary  Tract  ....  378 

Fever  Urine      37^ 

Urine  of  Chronic  Disease  (not  Renal)      379 

Typhoid  Fever 380 

Yellow  Fever 381 

Typhus  Fever 382 

Relapsing  Fever 382 

Pneumonia 383 

Pulmonary  Tuberculo.sis      384 

•    Malarial  Fever      .    .         385 

Erysipelas 3°^ 

Cholera 387 

Scarlet  Fever 388 

Diphtheria 39° 

Smallpox • 390 

Acute  General  Peritonitis 39 ^ 

Intestinal  Obstruction 39' 

Acute  Yellow  Atrophy  of  the  Liver 392 

Hysteria    .    .            393 

Cerebrospinal  Meningitis 393 

Melancholia 394 

Acute  Myelitis      394 

Epilepsy 395 

Acute  Articular  Rheumatism      395 

Gout      396 

Anemia 397 

Scurvv 397 


14  CONTENTS. 

PAGE 

Carbolic  Acid  Poisoning 398 

Poisoning  by  Phospliorus  and  Arseniureted  Hydrogen 398 


APPENDIX  A. 

Method  of  Recording  Urinary  Examinations 400 

Order  of  Applying  Tests 403 

Method  of  Making  Diagnoses  of  Diseases  of  the  Kidneys  from  the 

Urine 403 


APPENDIX  B. 

Reagents  and  Apparatus   for   Qualitative  and  Quantitative 

Analysis  of  Urine 406 

Liquid  Reagents 406 

Solid  Reagents 4°? 

Apparatus 407 

INDEX 409 


CLINICAL 

EXAMINATION  OF  THE  URINE 

AND 

URINARY  DIAGNOSIS. 


URINARY  ANALYSIS. 


INTRODUCTION. 

The  urine  is  an  aqueous  solution  of  organic  and  inor- 
ganic substances  excreted  and  secreted  by  glands  called 
the  kidneys.  Assuming  that  the  reader  is  acquainted  with 
the  gross  and  minute  structure  of  the  kidneys,  it  remains 
for  us  to  consider  some  of  the  physiologic  processes  which 
are  concerned  in  the  production  of  the  urine.  The  very 
close  relation  which  exists  between  the  blood-vessels  and 
the  uriniferous  tubules  suggests  at  once  the  fact  that  the 
fluid  called  urine  is  the  product  of  nature's  effort  to  re- 
move from  the  body,  by  way  of  the  blood,  those  substances 
which  are  no  longer  useful  to  the  tissues  of  the  body  ;  in 
other  words,  the  urine  is  essentially  a  solution  of  waste- 
products  of  the  body. 

Having  carefully  studied  the  minute  structure  of  the 
kidneys,  we  find  that,  unlike  other  secreting  organs,  they 
consist  of  two  parts,  so  distinct  in  structure  that  it  seems 
almost  impossible  to  resist  the  conclusion  that  their  func- 
tions are  different,  and  that  the  mechanism  by  which  the 
urine  is  secreted  is  of  a  double  kind.  The  uriniferous 
tubules,  on  the  one  hand,  with  their  characteristic  epithe- 
lium, appear  to  be  merely  secreting  structures  ;  while,  on 
the  other  hand,  the  Malpighian  capsules  with  their  glom- 
eruli are  structures  wdth  insignificant  epithelium,  strongly 
suggesting  that  their  function  is  rather  one  of  the  nature  of 
a  filter  than  of  a  secreting  structure.  Such  is  the  theory 
of  Bowman,  since  he  first  pointed  out  that  certain  constit- 
uents of  the  urine  only  are  put  forth  by  the  uriniferous 
tubules,  which  act  in  a  manner  similar  to  other  secreting 
glands,  and  that  the  other  constituents,  including  water 
and  various  soluble  and  diffusible  salts  from  the  blood,  are 
apparently  filtered  out  by  the  glomeruli.  It  is  very  evident 
from   the   vascular    arrangement    in    the    kidney   that    the 

2  17 


18  INTRODUCTION. 

capacity  of  the  kidney  for  work  is  closely  dependent  on  the 
flow  of  blood  through  it,  and  this  appears  to  be  controlled 
largely  by  the  vasomotor  and  vasodilator  nerves,  which  are 
supplied  by  the  anterior  roots  of  the  eleventh,  twelfth,  and 
thirteenth  dorsal  nerves. 

The  theory  of  Ludwig,  based  on  the  varying  degrees  of 
blood  pressure  in  the  glomeruli,  and  the  elimination  of  cer- 
tain constituents  of  the  blood  by  diffusion  or  osmosis,  can 
hardly  be  considered  tenable  in  the  light  of  recent  physi- 
ologic research.  In  this  theory  Ludwig  did  not  consider 
the  importance  of  the  renal  epithelium  in  the  secretion  of 
urine,  as  has  been  well  demonstrated  by  the  experiments 
of  Heidenhain,  who  found  that  by  injecting  a  solution  of 
sodium  indigo-sulphate  into  the  blood  of  an  animal  not 
only  the  urine  became  blue,  but  the  epithelial  cells  lining 
the  convoluted  tubules  and  the  looped  tubes  of  Henle 
were  also  colored  blue,  while  there  was  not  the  slightest 
trace  of  blue  in  the  Malpighian  bodies.  By  first  dividing 
the  spinal  cord  of  an  animal  and  J:hen  injecting  the  indigo 
solution,  he  also  demonstrated  the  fact  that  the  renal 
epithelium  has  distinct  eliminativ^e  power.  He  found  the 
following  :  That  no  urine  reached  the  bladder,  and  the  epi- 
thelium lining  the  convoluted  tubules  as  well  as  those  of 
Henle  was  stained  blue  the  same  as  before  ;  that  when  the 
animal  was  killed,  a  sufficient  period  after  the  injection,  the 
epithelium  was  found  to  be  free  from  coloring-matter,  and 
the  indigo  compound  had  passed  into  the  lumen  of  the 
tubules,  where,  in  the  absence  of  water  from  the  glomeruli, 
it  had  crystallized.  It  often  happens  in  some  diseases  of 
the  kidneys  in  which  the  renal  tubules  become  stripped  of 
their  epithelium  that  the  urea  and  other  products  of  the 
metabolism  are  no  longer  so  thoroughly  removed  from  the 
body,  but  remain  in  the  blood,  and  frequently  cause  the 
symptom  known  as  uremia,  often  when  the  watery  constit- 
uent is  eliminated  in  abundance. 

It  is,  therefore,  fair  to  conclude  that  the  renal  epithelial 
cells  are  normally  actively  engaged  in  the  process  of  secre- 
tion, and  that  the  water  and  some  of  the  soluble  salts  of 
the  urine  are  secreted  largely  by  the  glomeruli,  the  func- 
tion of  which  is  regulated  chiefly  by  the  varying  degrees 
of  blood  pressure. 

Too  much  can  not  be  said  regarding  the  importance  of 
an  accurate  examination  of  the  urine, — both  chemic  and 


INTRODUCTION.  19 

microscopic, — for  it  is  by  this  means  only  that  the  condi- 
tion of  the  kidneys — whether  healthy  or  diseased — and 
their  capability  for  work  can  be  definitely  determined. 
Furthermore,  by  the  correct  interpretation  of  the  results  of 
modern  methods  of  urinary  analysis,  the  variations  in  the 
body  metabolism — nutrition  and  waste — can  also  be  deter- 
mined, and  such  information  is  often  of  the  greatest  impor- 
tance to  the  physician  in  judging  of  the  diagnosis  and 
prognosis  of  disease.  While  it  is  impossible  to  diagnosti- 
cate all  diseases  from  an  examination  of  the  urine,  it  is, 
nevertheless,  a  fact  that  an  extensive  disease,  whether  in 
the  kidneys  or  not,  can  not  exist  in  the  human  organism 
without  showing  its  effect  in  the  urine.  This  is  more  espe- 
cially true  in  connection  with  diseases  and  disturbances  of 
the  kidneys,  when  any  deviation  in  the  urine  from  the  nor- 
mal furnishes  us  with  the  only  reliable  data  concerning  the 
nature  of  the  diseased  process. 

It  is,  therefore,  essential  that  the  practitioner  and  student 
of  medicine  should  become  perfectly  familiar  with  those 
features  of  the  urine  that  are  characteristic  of  certain  dis- 
eased conditions ;  and  also  to  become  acquainted  with 
those  alterations  of  the  urine  found  in  various  functional 
disturbances  of  the  body,  such  as  derangements  of  gastric 
and  intestinal  digestion,  etc. 

Nomenclature. — The  student  of  medicine  is  frequently 
confused  b)-  the  complicated  nomenclature  of  the  diseases 
of  the  kidneys.  He  finds  that  the  various  diseased  condi- 
tions of  these  organs  have  received  a  variety  of  names,  and 
that  the  terms  employed  indicate  a  number  of  pathologic 
conditions.  This  is  partly  due  to  the  fact  that  a  given 
cause  does  not  always  produce  the  same  anatomic  lesions 
in  the  kidneys,  and  partly  to  the  fact  that  a  marked  lack  of 
uniformity  exists  between  the  terms  used  by  the  pathologist 
and  those  used  by  the  clinician  in  the  description  of  any 
given  kidney  disease.  What  is  certainly  needed  are  more 
numerous  and  more  thorough  clinical  observations,  and, 
in  every  instance  possible,  a  careful  study  of  these  observa- 
tions in  connection  with  the  pathologic  findings. 

As  Councilman  ^  has  said  :  "  For  the  present,  the  classi- 
fication of  the  diffuse  lesions  of  the  kidney  must  be  founded 
on  the  character  of  the  anatomical  lesions.      A  classification 

'  "  American  Journal  of  the  Medical  Sciences,"  July,  1897. 


20  INTRODUCTION. 

on  an  etiological  basis  is  the  most  scientific  and  the  simplest, 
but  we  know  little  or  nothing  of  the  etiology  of  these  dis- 
eases. Various  forms  of  disease  in  other  organs,  partic- 
ularly of  the  heart,  are  often  found  associated  with  them. 
Bacteriological  investigation  has  shown  in  many  cases  the 
presence  of  certain  organisms  in  the  kidney.  In  most 
cases  the  bacteria  are  found  in  some  other  lesions  and  in 
the  blood,  and  their  presence  in  the  kidney  is  but  a  part  of 
a  general  septicemia.  Moreover,  the  same  condition  in 
the  kidney  may  be  associated  with  a  variety  of  organisms, 
and  the  same  organism  may  be  associated  with  widely  dif- 
ferent anatomical  lesions." 

The  nomenclature  which  the  author  has  adopted  in  this 
work  is  calculated  to  be  abreast  with  recent  pathologic 
investigation.  The  term  cJironic  parciicJiyniatous  nephritis, 
which  was  introduced  by  Virchow  (1852),  has  been  re- 
placed by  the  term  subacute  glomerular  nephritis.  This 
change  is  based  upon  the  fact  that  the  lesion  which  was 
formerly  thought  to  be  confined  to  the  epithelial  constit- 
uents of  the  kidney  has  recently  been  found  to  involve 
chiefly  the  glomeruli ;  also  because  the  disease  is  sub- 
acute rather  than  chronic  in  duration. 

In  the  use  of  the  word  nephritis  it  must  be  understood 
that  the  lesions  referred  to  are  not  necessarily  inflamma- 
tory ;  while  inflammatory  exudation  in  some  form  is  fre- 
quently present,  it  is  safe  to  say  that  the  majority  of  lesions 
of  the  kidneys  are  not  inflammatory. 

We  shall  frequently  refer  to  diffuse  lesions  of  the  kidney, 
such  as  acute  diffuse  nephritis  and  chronic  diffuse  nephri- 
tis. By  the  term  diffuse  we  do  not  mean  that  all  parts  of 
the  kidney  are  equally  affected.  It  has  been  demonstrated, 
by  the  study  of  degenerations  and  the  effect  of  poisons, 
that  in  some  instances  the  most  marked  changes  are  in  the 
convoluted  tubules,  while  in  others  they  are  in  the  loops 
of  Henle  or  in  the  collecting  tubules.  All  parts  of  the 
kidney  are  equally  exposed  to  the  action  of  chemic  irri- 
tants, but  all  may  not  be  equally  susceptible.  Likewise,  in 
glomerular  lesions  of  the  kidney  the  accompanying  degen- 
erative lesions  in  the  renal  epithelium  may  be  in  part  or 
wholly  secondary  to  the  lesions  of  the  glomeruli.  In  other 
words,  in  diffuse  lesions  of  the  kidney  various  parts  of  the 
organ  may  be  primarily  or  secondarily  affected,  but  usually 
not  all  parts  are  affected  to  the  same  extent. 


CHAPTER  I. 

CONSTITUENTS  OF  NORMAL  URINE» 

The  complexity  of  the  urine  eHminated  under  normal 
conditions  is  well  shown  by  the  following  classification  of 
Hoppe-Seyler  : 

1.  Urea  and  allied  substances :  Uric  acid,  allantoin, 
oxalic  acid,  xanthin,  guanin,  kreatinin,  and  thio-  (sulpho-) 
cyanic  acid, 

2.  Fatty  and  other  nonnitrogenous  substances  :  Fatty 
acids  of  the  series  C.iHj^Oj ;  oxalic,  lactic,  glycerophos- 
phoric  acids  ;  minute  quantities  of  certain  carbohydrates  (?). 

3.  Aromatic  substances:  The  ethereal  sulphates  of  phe- 
nol, kresol,  pyrocatechin,  indoxyl,  and  skatoxyl  ;  hippuric 
acid  ;  aromatic  oxyacids. 

4.  Other  organic  substances  :  Pigments  ;  ferments,  espe- 
cially pepsin  ;  mucous  and  humous  substances  ;  kynurenic 
acid. 

5..  Inorganic  salts  :  Chlorides  of  sodium  and  potassium  ; 
potassium  sulphate ;  sodium,  calcium,  and  magnesium 
phosphates  ;  silicic  acid  ;  ammonia  compounds,  and  cal- 
cium carbonate. 

6.   Gases  :  Nitrogen  and  carbonic  acid. 

Quantitative  Composition  of  Normal  Urine. — A  num- 
ber of  estimations  of  the  constituents  of  normal  urine  have 
been  made,  but  the  following  table  by  Parkes  gives  the 
most  accurate  determination  thus  far  known  : 

AMOUNTS  OF  URINARY  CONSTITUENTS  ELIMINATED  IN 
TWENTY-FOUR  HOURS  (PARKES). 

By  an  Average  Man  Weigh-       Per  Kilogram  of 
Constituents.  ing  Sixty-six  Kilograms.  Body-weight. 

Water 1500.00  grams.  23.000  grams. 

Total  solids 72.00      "  1. 100      " 

Urea 33- 18      "  0.500      " 

Uric  acid 0.55       "  0.008      " 

Hippuric  acid 0.40      "  0.006      " 

21 


22  CONSTITUENTS  OF  NORMAL  URINE. 

AMOUNTS   OF   URINARY  CONSTITUENTS  ELIMINATED  IN 
TWENTY-FOUR  HOURS  (PKKK.Y.?,).  — {Continued.) 

By  an  Average  Man  Weigh-      Per  Kilogram  of 
Constituents.  ing  Sixty-six  Kilograms.  Body-weight. 

Creatinin 0.91  grams.                    0.014  grains. 

Pigment   and   other  organic   sub- 
stances       10.00  "                          o.  151       " 

Sulphuric  acid 2.01  "                          0.030      " 

Phosphoric  acid 3.16  "                          0.048       " 

Chlorine 7-8.00  "                          0.126      " 

Ammonia 0.77  " 

Potassium 2.50  " 

Sodium 11.09  "                            •    • 

Calcium 0.26  " 

Magnesium 0.21  "                          .    . 

Yvon  and  Berlioz  ^  have  carefully  studied  the  urines  of 
both  male  and  female,  and  have  constructed  the  following 
comparative  table,  which  includes  the  amounts  of  some  of 
the  more  important  urinary  solids,  excepting  chlorides  : 

Male.  Female. 

Quantity  (per  diem) 1360      c.c.  iioo      c.c. 

Specific  gravity 1022       "  1021        " 

Urea  (per  liter) 21.5  grams  19. 0    grams 

"     (per  diem) 25.6      "  20.5        '< 

Uric  acid  (per  liter) 0.5      "  0.55      " 

•'       "    (per  diem) 0.6       "  0.57      " 

Phosphoric  acid  (per  liter) 2.5      "  2.4       " 

"             "    (per  diem)      3.2      "  2.6       " 

Collection  of  Urine  for  Analysis. — The  whole  quantity 
of  urine  for  twenty-four  hours  should,  in  all  cases,  be  col- 
lected, thoroughly  mixed,  and  carefully  measured.  If  the 
entire  secretion  for  twenty-four  hours  can  not  be  conven- 
iently submitted  for  analysis,  a  sample  (from  four  to  eight 
ounces)  of  the  mixed  urine,  together  with  a  statement  of  the 
quantity  eliminated  in  twenty-four  hours,  will  suffice. 

A  four  or  five  pint  bottle,  perfectly  clean,  is  perhaps  the 
most  convenient  receptacle  for  the  urine  during  its  collec- 
tion. The  botde  should  be  well  corked  after  each  addition 
of  the  urine,  and  should  stand  in  a  cool  place.  The  urine 
should  never  be  collected  or  allowed  to  stand  in  an  open 
or,  above  all,  in  an  unclean  vessel.  Every  effort  should  be 
made  to  avoid  the  introduction  of  particles  of  dust,  fecal 
matter,  expectorated  matter,  and  the  like,  all  of  which  seri- 
ously interfere  with  the  subsequent  analysis  of  the  urine, 

1  "Lancet,"  vol.  11,  1888,  p.  629. 


COLLECTION  OF  URLXE.  23 

It  should  be  borne  in  mind  that  the  urine  begins  to  un- 
dergo the  process  of  decomposition  within  a  few  hours  after 
it  has  been  v^oided,  although  the  changes  are  usually  very 
slight  and  unimportant,  providing  the  urine  is  kept  cool. 
In  order,  however,  to  guard  against  decomposition  of  the 
urine  during  its  collection,  it  is  advisable  to  put  into  the 
bottle  one  ounce  of  a  cold  saturated  aqueous  sohition  of  boric 
acid  (about  four  per  cent.),  or  tivo  or  three  drops  of  formalin 
(not  more) ;  stopper  tightly,  and  then  add  the  urine  imme- 
diately after  each  micturition.  The  ounce  of  boric  acid 
solution  is  to  be  deducted  from  the  total  quantity  of  urine 
when  it  is  measured. 

A  convenient  time  to  begin  to  save  the  urine  is  at  7  a.  m. 
At  that  hour,  or  such  other  time  as  may  be  decided  upon, 
the  bladder  should  be  emptied,  and  the  urine  thrown  away  ; 
then  all  the  urine  voided  in  the  subsequent  twenty-four 
hours,  including  the  amount  of  urine  in  the  bladder  at  7 
A.  M.  the  next  day,  will  represent  the  total  quantity  for 
twenty-four  hours.  It  is  often  important  to  collect  the  day 
and  )iight  urine  separately  ;  in  such  cases  the  urine  voided 
between  7  a.  m.  and  7  p.  m.  is  to  be  placed  in  one  bottle, 
and  that  voided  between  7  p.  m.  and  7  a.  :ni.  in  another 
bottle,  carefully  labeling  each. 

For  the  qualitative  exannnation  a  single  specimen  of 
urine,  the  product  of  one  micturition,  may  be  collected. 
Since  there  is  a  marked  variation  in  the  urine  at  different 
times  of  day,  a  specimen  should  be  taken  at  a  time  when 
the  urine  is  most  likely  to  contain  the  largest  proportion 
of  morbid  elements — /.  c.,  about  midday  or  between  three 
and  four  hours  after  a  meal.  For  the  purpose  of  compari- 
son such  a  sample  should,  however,  always  be  accom- 
panied by  another  specimen  collected  in  the  morning  on 
rising — /.  e.,  at  a  time  when  the  urine  contains  the  smallest 
proportion  of  abnormal  elements.  As  previously  indicated, 
the  urine  should  always  be  poured  into  a  perfectly  clean 
bottle,  and  should  be  submitted  for  examination  in  a  per- 
fectly fresh  condition, — that  is,  before  decomposition  has 
begun, — since  the  morphologic  elements,  such  as  casts, 
epithelium,  etc.,  in  a  urine  that  has  decomposed  may  dissolve 
or  become  so  altered  that  they  are  beyond  recognition. 


24  CONSTITUENTS  OF  NORMAL  URINE. 

PHYSICAL  PROPERTIES  OF  THE  URINE. 

Quantity. — For  a  healthy  adult  the  average  quantity  of 
urine  in  twenty -four  hours  is  1500  c.c,  or  about  50  fluid- 
ounces.  The  normal  variation  is  between  1200  and  1600 
c.c,  according  to  the  size,  habits,  and  sex  of  the  individ- 
ual— for  example,  a  female  of  average  size  usually  passes 
less  urine  in  twenty-hours  than  an  averaged-size  male. 
Furthermore,  a  small  adult,  male  or  female,  may  not  elimi- 
nate more  than  1200  c.c,  and  yet  be  in  a  state  of  perfect 
health.  The  habits  of  the  person  have,  perhaps,  the 
greatest  influence  on  the  twenty-four-hour  quantity  in 
health  ;  the  habitual  ingestion  of  considerable  quantities  of 
liquids,  liberal  eating,  and  the  like,  may  cause  the  quantity 
to  reach  1600  c.c,  or  even  more.  On  the  other  hand, 
exercise,  free  perspiration,  the  ingestion  of  very  little  liquid, 
may  result  in  the  elimination  of  a  small  quantity  of  urine, 
even  below  1200  c.c. 

The  quantity  of  urine  in  health  varies  considerably  with 
the  time  of  day,  the  largest  amount  being  passed  in  the 
afternoon,  the  least  at  night,  and  the  mean  quantity  in  the 
forenoon. 

The  total  quantity  of  urine  for  twenty-four  hours  should 
be  accurately  measured  in  every  case  in  which  the  urine  is 
to  be  examined,  and  it  is  frequently  necessary,  particularly 
in  disease  of  the  kidneys,  to  measure  the  urine  every  day 
for  a  period  of  one,  two,  or  three  weeks,  in  order  to  ascer- 
tain the  average  daily  quantity.  Upon  the  total  quantity 
depend  all  quantitative  determinations,  and,  therefore,  intelli- 
gent inferences  as  to  the  capability  of  the  kidneys  for  work. 

Diminished  Quantity. — A  diminished  quantity  of  urine 
in  twenty -four  hours — that  is,  less  than  i  500  c.c. — has  the 
following  causes  :  (i)  Small  quantity  of  liquid  taken  ;  (2) 
free  perspiration  ;  (3)  fever ;  (4)  diarrhea  ;  (5)  vomiting,  and 
the  following  renal  disturbances  and  diseases  :  (6)  most 
cases  of  active  hyperemia  ;  (7)  passive  hyperemia ;  (8)  first 
and  second  stages  of  acute  diffuse  nephritis  ;  (9)  subacute 
glomerular  nephritis  ;   (10)  toward  death  in  all  diseases. 

Increased  Quantity. — The  causes  of  an  increased  quan- 
tity of  urine  in  twenty-four  hours  are  as  follows:  (i) 
Large  quantity  of  liquid  taken  ;  (2)  diuretic  treatment ; 
(3)  nervous  excitement  and  some  diseases  of  the  nervous 
system  (frequently  in  hysteria,  and  temporarily  in  cerebral 


COLOR  OF  URINE.  25 

hemorrhage) ;  (4)  diabetes  melHtus  ;  (5)  diabetes  insipidus  ; 
(6)  convalescence  from  acute  diseases  in  general,  and  the 
following  disturbances  and  diseases  of  the  kidneys  :  (7) 
convalescence  from  a  severe  active  hyperemia ;  (8)  con- 
valescence from  an  acute  diffuse  nephritis  ;  (9)  chronic  inter- 
stitial nephritis  ;  (10)  chronic  diffuse  nephritis  ;  (i  i)  amyloid 
infiltration. 

Oliguria  is  the  term  applied  to  those  cases  in  which  the 
quantity  of  urine  is  very  small,  typically  seen  during  the 
acute  stage  of  an  acute  disease,  also  in  those  chronic  dis- 
eases that  are  attended  with  extensive  dropsy. 

Anuria  is  applied  to  cases  in  which  there  is  no  urine,  or 
when  only  an  exceedingly  small  quantity  is  passed — in 
other  words,  complete,  or  almost  complete,  supprcssio)i  of 
uri)ic.  This  condition  is. most  commonly  seen  shortly  be- 
fore death,  particularly  in  extensive  disease  of  the  kidneys. 
Total,  or  nearly  total,  suppression  may  last  several  days — 
from  five  to  ten. 

Polyuria  is  a  term  signifying  the  excretion  of  a  large 
quantity  of  urine  without  any  reference  to  the  quantity  of 
total  solids  in  twenty-four  hours.  Hydruria  is  a  term 
signifying  the  excretion  of  a  large  amount  of  urine — in  other 
words,  a  polyuria — with  either  a  normal  quantity  or  a 
diminution  in  the  total  solids  for  twenty -four  hours  :  for 
example,  in  marked  cases  of  chronic  interstitial  nephritis, 
the  solids  are  notably  diminished. 

Obstructive  suppression  occurs  when  there  is  a  partial 
or  complete  obstruction  to  the  outflow  of  urine  through 
the  ureters,  and  is  sometimes  found  to  be  due  to  the  pres- 
ence of  impacted  calculi  in  both  ureters  ;  also  to  the  pres- 
sure of  a  new  growth,  and  occasionally  by  valves  or  twists 
of  the  ureters.  In  a  case  reported  by  Farlow^  obstruction 
was  caused  by  a  new  growth  of  the  uterine  appendages, 
and  almost  complete  obstruction  lasted  for  twelve  days. 

Retention  of  urine  is  the  result  of  an  obstruction  to  the 
outflow  of  urine  through  the  urethra,  as  by  a  tight  urethral 
stricture,  the  presence  of  a  calculus  in  the  urethra,  or  by 
some  mechanical  obstruction  in  the  region  of  the  neck  of 
the  bladder. 

Color. —  I.  The  color  of  the  urine  under  normal 
conditions    is    straw   or    amber    yellow.      This,    however, 

^  J.  W.  Farlow,  "Boston  Medical  and  Surgical  Journal,"  cxx,  p.  333. 


26  CONSTITUENTS  OF  NORMAL  URINE. 

varies  considerably  even  within  the  range  of  perfect  health. 
The  color  may  be  said  to  vary  with  the  dilution  or  concen- 
tration of  the  urine.  Thus,  a  very  dilute  urine  has  a  pale 
color  and  may  be  almost  colorless,  containing  a  relatively 
small  amount  of  coloring-matter,  and  in  health  is  usually 
the  result  of  copious  drinking.  On  the  other  hand,  a  con- 
centrated urine  usually  has  a  Jiigli  color,  contains  a  relative 
excess  of  the  normal  coloring-matter,  and  is  seen  when  too 
little  water  is  taken,  also  after  free  perspiration  and  vigor- 
ous exercise.  It  is  evident,  therefore,  that  in  health  the 
color  may  range  from  a  very  pale  or  watery  color  through 
the  yellows  to  a  high  or  deep  red.  For  practical  purposes 
the  color  may  be  termed  pale,  normal,  and  high,  according 
to  circumstances. 

Vogel  has  constructed  a  scale  of  colors  of  the  urine  from 
nature.  (See  Frontispiece.)  These  colors  are  expressed 
as  (i)  pale  yellow;  (2)  light  yellow;  (3)  yellow;  (4) 
reddish-yellow  ;  (5)  yellowish-red  ;  (6)  red  ;  (7)  brownish- 
red  ;  (8)  reddish-brown  ;  (9)  brownish-black.  Vogel  classi- 
fies these  colors  into  groups  of  three  ;  the  first  three  being 
yellow,  the  second  three  being  red,  and  the  last  three 
brown  or  black.  In  applying  the  chart  the  urine  should 
first  be  filtered  if  not  already  perfectly  transparent.  It 
should  then  be  poured  into  a  glass  vessel  at  least  three  or 
four  inches  in  diameter,  and  examined  by  transmitted  light. 
This  color  chart  is  of  considerable  value  as  a  means  for 
comparison. 

2.  {(.i)  Under  pathologic  conditions  there  is  a  greater 
variation  than  in  health,  the  color  being  due  either  to  an 
increase  or  diminution  of  the  normal  pigments,  or  to  the 
addition  of  one  or  more  pathologic  coloring-matters.  Very 
pale  urines  are  usually  attended  with  a  large  quantity 
of  urine,  as  in  chronic  interstitial  nephritis,  chronic  dif- 
fuse nephritis,  amyloid  infiltration,  well-advanced  convales- 
cence from  acute  nephritis,  diabetes  mellitus,  and  diabetes 
insipidus.  On  the  contrary,  the  urine  may  have  a  pale 
color  with  a  diiniuished  quantity  of  urine,  as  in  the  inactive 
stage  of  subacute  glomerular  nephritis,  and  in  certain 
chronic  affections  elsewhere  in  the  body,  particularly  those 
accompanied  by  marked  diminution  in  the  normal  solids  in 
the  urine. 

The  urine  may  have  a  normal  color  in  certain  pathologic 
conditions,  particularly  in  active  hyperemia  of  the  kidneys, 


COLOR  OF  URlxN'E.  27 

frequentl)-  in  the  early  stage  of  chronic  interstitial  nephritis, 
and  rarely  in  subacute  glomerular  nephritis.  Occasion- 
ally, in  diabetes  mellitus  when  the  quantity  of  urine  is  in- 
creased to  three  or  four  liters,  the  color  is  normal,  the 
result  of  an  absolute  increase  of  the  coloring-matters. 

Urines  having  a  Jugh  color  are  almost  invariably  seen  in 
the  early  stage  of  acute  disease,  also  usually  in  active  and 
passive  hyperemia  of  the  kidneys,  active  stage  of  subacute 
glomerular  nephritis,  and  in  certain  diseases  elsewhere  in 
the  bod}',  notably  liver  diseases,  acute  articular  rheumatism, 
and  frequently  in  cases  of  chronic  rheumatism  and  chronic 
gout. 

From  the  foregoing  it  is  seen  that,  either  in  health  or 
disease,  the  urine  may  be  pale,  iioruial,  or  highly  colored ; 
consequently,  as  far  as  the  color  alone  is  concerned,  only 
negative  inferences  can  be  deduced  concerning  the  existing 
pathologic  condition. 

[b)  A  dark  or  smoky  urine  should  always  be  recog- 
nized, for  it  invariably  indicates  the  presence  of  an  ab- 
normal pigment.  Great  care  should  be  taken  not  to 
confound  a  dark  color  with  a  high  color.  This  abnormal 
pigment  is  most  commonly  found  to  be  decomposed  blood 
pigment  (methemoglobin  or  hematin),  although  it  is  fre- 
quently seen  after  carbolic  acid  has  been  taken,  and  occa- 
sionally after  its  use  as  an  external  application.  It  is  also 
occasionally  seen  after  the  use  of  pJienol  compounds, 
especially  certain  drugs,  such  as  salol  (when  taken  in  large 
doses),  guaiacol,  etc.  A  urine  after  the  ingestion  of  phenol 
is  usually  normal  in  color  when  passed,  but  on  standing 
exposed  to  the  air  soon  becomes  dark,  and  may,  if  allowed 
to  stand  a  still  longer  time,  become  almost  black — the 
result  of  the  decomposition  product  of  the  phenol  (hydro- 
chinone).  A  urine  containing  bile  pigment  in  the  form  of 
bilirubin  often  has  a  dark  color  ;  when  such  a  urine  is 
shaken,  the  foam  will  be  found  to  have  a  decided  yellow  or 
greenish-yellow  color,  and  as  the  urine  stands  exposed  to 
the  air,  it  soon  takes  on  a  greenish,  and  if  much  bile  is 
present  a  marked  green,  color.  The  presence  in  the  urine 
of  an  abnormal  pigment  called  melanin  may  cause  a  dark 
urine  ;  the  freshly  passed  urine  usually  has  a  normal  color, 
but  on  standing  exposed  to  the  air  it  gradually  grows 
darker  from  above  downward,  due  to  the  slow  oxidation  of 
the  chromogen, — melanogen, — which  results  in  the  pigment 


28  CONSTITUENTS  OF  NORMAL  URINE. 

melanin.  Alcaptoii,  which  has  a  strong  affinity  for  oxygen, 
produces  a  dark-colored  urine.  The  urine  is  usually  normal, 
or  high  in  color,  when  passed,  but  on  standing  exposed  to 
the  air  rapidly  absorbs  oxygen,  and  a  dark  color  results. 

(c)  A  black  urine  is  generally  produced  by  unusually 
large  amounts  of  those  substances  which  cause  a  dark  or 
smoky  urine,  particularly  methemoglobin,  melanin,  and 
alcapton. 

{li^  A  bloody  urine  indicates  the  presence  of  normal 
blood  and  its  pigment,  oxyhemoglobin.  A  urine  which  has 
a  slightly  bloody  tint  should  always  be  distinguished  from 
one  having  a  high  color. 

{e)  A  blue  urine  is  of  very  rare  occurrence.  It  is  due  to 
the  presence  of  free  indigo,  a  result  of  the  decomposition 
of  the  indoxyl,  which,  in  all  such  instances,  is  present  in 
enormous  quantity.  Blue  urine  has  been  seen  in  cholera 
and  rarely  in  typhus  fever.  When  methylene-blue  is  taken 
into  the  stomach,  it  is  absorbed  and  eliminated  in  the  urine, 
to  which  it  gives  a  marked  blue  or  green  color. 

(/)  Urines  having  a  greenish  tint  are  occasionally  seen, 
particularly  after  the  use  of  an  abundant  quantity  of  milk, 
also  in  the  inactive  stage  of  a  subacute  glomerular  ne- 
phritis, chronic  diffuse  nephritis,  amyloid  infiltration,  and 
in  some  diabetic  urines  with  a  high  percentage  of  sugar.  As 
previously  mentioned,  a  urine  containing  bile  may,  after  the 
bilirubin  has  become  oxidized,  have  a  marked  green  color. 

iyg)  The  urine  frequently  has  an  abnormal  color  after 
the  ingestion  of  certain  vegetable  substances,  such  as  santonin, 
which  imparts  a  yellow  color,  and  rhubarb  and  senna,  which 
cause  a  brown  or  reddish  color. 

The  following  table  of  Halliburton  ^  shows  the  nature 
and  origin  of  the  chief  variations  in  tint : 

Color.  Cause  of  Color.  Pathologic  Condition. 

Nearly  colorless.  Dilution  or  diminution  of      Various   nervous    condi- 

normal  pigments.  tions,    hydruria,     dia- 

betes insipidus,  granu- 
lar kidney. 
Dark  yellow  tobrown-       Increase  of  normal  or  oc-       Acute  febrile  diseases, 
red.  currence  of  pathologic 

pigments. 
Milky.  Fat  globules.  Chyluria. 

Pus  corpuscles.  Purulent  disease  in  urin- 

ary tract. 

^  "Chemical  Physiology,"  1841,  p.   712. 


TRANSPARENCY. 


29 


Color. 


Orange. 

Red  or  reddish. 


Brown      to      brown- 
black. 


Greenish-yellow, 
greenish-brown, 
approaching  black. 

Dirty  green  or  blue. 


Brown-yellow  to  red- 
brown,  becomes 
blood-red  on  addi- 
tion of  alkalies. 


Cause  of  Color. 
Excreted  drugs,  e.  g. , 

Unchanged  hemoglobin. 

Pigments  in  food  (log- 
wood, madder,  bilber- 
ries, fuchsin). 

Hematin. 

Methemoglobin. 

Melanin. 

Hydrochinone  and  cate- 
chol. 

Bile  pigments. 


A  dark  blue  scum  on  sur- 
face with  a  blue  de- 
posit, due  to  excess  of 
indigo  -  forming  sub- 
stances. 

Substances  introduced 
into  the  organism  with 
senna,  rhubarb,  and 
chelidonium. 


Pathologic  Condition. 

Santonin,  chrysophanic 
acid. 

Hemorrhage  or  hemo- 
globinuria. 


Small  hemorrhages. 
Methemoglobinuria. 
Melanotic  sarcoma. 
Carbolic  acid  poisoning. 


Jaundice. 


Cholera,  typhus  ;  seen 
especially  when  the 
urine  is  putrefying. 


Transparency.— Freshly  passed  normal  urine  is  gener- 
ally a  perfectly  transparent  fluid  ;  as  far  as  can  be  deter- 
mined by  inspection,  it  is  free  from  solid  suspended  mat- 
ter     After  such  a  urine  has  stood  a  short  time  (one-half 
to  four  hours),  however,  a  light  flocculent  cloud,  consisting 
of  mucus,  cells,  etc.,  will  be  found  to  occupy  the_  center  of 
the  column  of  urine,  and  if  the  urine  be   not   highly  con- 
centrated, it  usually  settles  to  the  bottom  of  the  urine  glass. 
This  flocculent  cloud  is  generally  not  sufficient  to  render 
the  urine  turbid.     A  perfectly  normal,  freshly  passed  urme, 
may   however,  be  turbid  and  have  a  milky  appearance,  due 
to  a  precipitation  of  earthy  phosphates.     Such  a  urine  is 
frequently  seen  after  a  hearty  meal,  especially  following  the 
ingestion  of  vegetable  food,  and  is  the  result  of  the  elimina- 
tion of  the  alkaline  salts  of  the  food.-alkaline  carbonates, 
—which  render  the  urine  neutral  or  alkaline,  and  precipitate 
the   earthy   phosphates ;    it   is   perfectly   physiologic     and 
usually  of  short  duration,  lasting  only  two  to  three  hours 
when  the  urine  again  becomes  clear  and   transparent.      A 
urine  turbid  from  phosphates  may  be  temporarily  seen  alter 
every  meal  ;  but,  on  the  other  hand,  in  some  individuals 
the  after-meal  urine  is  rarely,  if  ever,  turbid  from  this  cause. 
Any  urine  which   is   permanently  turbid  at  the  time  it  is 
voided  may  safely  be  considered  pathologic. 


30  CONSTITUENTS  OF  NORMAL  URINE. 

The  total  twenty-four-hour  urine  should  in  all  cases  be 
perfectly  clear  and  transparent.  A  clear,  freshly  pas.sed 
normal  urine  may,  after  it  becomes  cool,  and  especially  if 
allowed  to  stand  in  a  cool  or  cold  place,  become  turbid  by 
the  separation  of  amorphous  urates,  which  soon  settle  to  the 
bottom  of  the  glass  and  form  an  abundant,  usually  pink, 
sediment.  This  deposit  of  urates  is  most  often  seen  in 
highly  concentrated,  although  perfectly  normal,  urines.  It 
may,  however,  be  seen  in  the  urines  of  disease,  as  in  respi- 
ratory and  circulatory  diseases,  and  also  in  the  active  stage 
of  subacute  glomerular  nephritis.  A  deposit  of  amorphous 
urates  is  readily  dissolved  upon  the  application  of  heat. 

Bacteria  frequently  cause  a  marked  turbidity  in  urines, 
and  especially  albuminous  urines  which  have  stood  some 
time  exposed  to  the  air.  The  urine  furnishes  a  favorable 
medium  for  the  growth  of  bacteria,  and  often  within  twelve 
hours  from  the  time  the  urine  was  passed  it  will  be  rendered 
very  turbid.  Such  urines  do  not  settle  well,  if  at  all,  prob- 
ably owing  to  the  constant  motion  of  the  bacteria.  Fur- 
thermore, bacteria  can  not  be  removed  by  filtration  through 
ordinary  filter-paper,  the  filtrate  being  usually  as  turbid  as 
the  unfiltered  urine. 

A  urine  which  has  undergone  alkali)ic  dccompositio)i  is 
generally  rendered  turbid  by  both  bacteria  and  earthy 
phosphates  ;  such  permanently  alkaline  urines  should  be 
distinguished  from  tho.se  temporarily  alkaline  (after-meal 
urines)  ;  the  former  being  ammoniacal,  while  the  latter  are 
alkaline  from  fixed  alkalies  (absence  of  ammonia). 

A  urine  containing  a  large  amount  of  pus  is  invariably 
turbid  from  the  pus  in  suspension.  Purulent  urines  also 
usually  contain  bacteria,  which  are  either  present  when  the 
urine  is  passed  or  grow  very  rapidly  when  the  urine  is 
allowed  to  stand  exposed  to  the  air. 

Chyle  in  the  urine  causes  a  milky  turbidity,  due  to  the 
presence  of  very  finely  divided  fat.  Such  a  urine  is  of  rare 
occurrence.      (See  Chyluria.) 

Odor. — Normal  urine  usually  has  a  pleasant,  aromatic 
odor,  due,  it  is  believed,  to  the  presence  of  extremely  small 
quantities  of  volatile  acids — phenylic,  taurylic,  damaluric, 
and  damolic  acids.  This  aromatic  odor  is  most  marked  in 
urines  which  are  concentrated.  The  so-called  "  urinous 
odor"  is  due  to  the  products  of  decomposition,  and  is  a 
putrescent,  repulsive  odor,  in  which  ammonia  is  plainly  dis- 


REACTION.  31 

tinguishable  ;  all  urines,  if  allowed  to  decompose,  have  a 
urinous  odor.  An  ammoniacal  or  urinous  odor  is  only  im- 
portant when  it  is  present  at  the  time  the  urine  is  passed, 
thus  showing  that  the  urine  has  decomposed  inside  the 
body.  When  a  urine  containing  a  large  amount  of  albumin 
or  a  large  quantity  of  pus  decomposes,  it  may  evolve  the 
odor  of  sulphuretted  hydrogen,  which  is  formed  from  the 
sulphur  in  the  albuminous  matter.  The  H2S  in  ammoni- 
acal urine  combines  with  the  ammonium  to  form  ammo- 
nium sulphide,  hence  the  combined  odor  of  sulphuretted 
hydrogen  and  ammonium. 

A  strong  odor  of  sulphuretted  hydrogen  to  the  urine 
may  accompany  the  evacuation  of  an  abscess,  located  in  the 
region  of  the  intestine,  into  the  urinary  tract ;  a  purulent 
urine  from  this  cause  usually  has  also  a  distinct  fecal  odor. 
When  urines  containing  cystin  decompose,  HgS  is  evoked, 
formed  from  the  sulphur  in  the  cystin. 

The  urine  frequently  has  a  peculiar  odor  after  the  inges- 
tion of  certain  vegetable  substances  and  certain  drugs ; 
thus,  it  has  a  characteristic  odor  after  eating  asparagus, 
and  an  odor  of  violets  following  the  inhalation  of  the 
vapor  of  oil  of  turpentine,  or  following  its  absorption  from 
the  skin  or  digestive  tract.  The  absorption  of  terebene 
gives  to  the  urine  the  same  odor  of  violets.  The  urine  has 
a  peculiar  odor  after  the  use  of  copaiba,  sandalwood  oil, 
cubebs,   tolu,  etc. 

The  odor  of  the  freshly  passed  urine  is  of  very  little  clin- 
ical importance,  excepting  in  those  instances  in  which  it  is 
ammoniacal  or  evolves  the  odor  of  sulphuretted  hydrogen. 

Reaction. — The  reaction  of  the  normal,  twenty-four- 
hour,  mixed  urine  is  ahva\-s  acid.  This  acidity  is  due 
to  acid  sodium  phosphate  (monosodic  acid  phosphate, 
NaH2P04).  It  is  believed  that  the  monosodic  acid  phos- 
phate of  the  urine  is  partly  derived  from  a  chemic  combi- 
nation taking  place  between  the  disodic  acid  phosphate 
(Na2HP04,  neutral  or  alkaline  in  reaction)  in  the  blood, 
and  uric  acid,  also  in  the  blood,  according  to  the  following 
equation  : 

Na^HPO,  ~  H.CjH.X.O,  =  NaH^PO,  -f  NaHC-H^NPj. 

It  was  formerly  supposed  that  traces  of  uric  and  hippuric 
acids  contributed  to  the  acidity  of  the  urine,  but  such  is 
probably  not  the  case,  as  has  been  shown  by  the  experi- 


32  CONSTITUENTS  OF  NORMAL  URINE. 

ments  of  Voit,  Huppert,  Briicke,  and  others,  who  found 
that  both  uric  and  hippuric  acids  existed  in  combination, 
the  former  as  a  urate  and  the  latter  as  a  hippurate. 

The  degree  of  acidity  varies  considerably  at  the  different 
hours  of  the  day,  and  particularly  with  the  length  of  time 
before  or  after  taking  food.  Usually,  a  specimen  of  urine 
passed  at  any  time  of  day  is  acid,  excepting  after  a  meal, 
when  it  may  be  temporarily  neutral  or  alkaline  from  fixed 
alkalies — alkaline  carbonates — which  are  derived  from  the 
salts  ingested  with  the  food.  This  temporary  change  in 
the  reaction  is  sometimes  called  the  alkaline  tide,  beginning 
with  a  gradual  diminution  of  the  acidity,  then  becoming 
neutral  or  alkaline,  reaching  its  height  in  from  two  to  four 
hours,  and  finally  becoming  acid  again.  This  is  a  physi- 
ologic condition  occurring  in  individuals  who  are  perfectly 
healthy.  Such  a  urine  is  generally  turbid  from  the  deposit 
of  earthy  phosphates  ;  the  addition  of  a  few  drops  of  acetic 
acid  to  the  urine  wall  readily  cause  the  turbidity  to  disappear 
entirely.  The  urine  may  be  highly  acid,  especially  after 
a  fast, — for  instance,  before  breakfast, — when  it  is  usually 
found  to  be  concentrated,  having  a  high  specific  gravity  and 
high  color.  Under  normal  conditions  the  freshly  passed 
urine  may  be  faintly  acid,  normally  acid,  or  strongly  acid, 
and  in  a  general  way  it  may  be  said  that,  with  the  excep- 
tion of  the  after-meal  urine,  the  degree  of  acidity  depends 
largely  upon  the  concentration — that  is,  if  dilute,  it  is  faintly 
acid,  and  if  highly  concentrated,  strongly  acid. 

A  urine  that  is  acid  when  passed,  upon  standing  exposed 
to  the  air  for  from  six  to  twelve  hours  often  becomes  more 
acid  ;  this  phenomenon  has  been  termed  acid fcrnientatioji. 
This  increased  acidity  has  been  ascribed  by  Sherer  to  the 
presence  of  lactic  and  acetic  acids,  formed  by  the  decompo- 
sition of  the  coloring-matters  of  the  urine  ;  the  decompos- 
ing element  being  mucus,  which  acts  as  a  ferment.  This 
explanation  has  not  been  satisfactorily  proved,  however, 
while  the  increased  acidity  is  by  no  means  constant.  A 
urine  that  has  undergone  this  so-called  acid  fermentation 
is  usually  higher  in  color  than  when  it  was  passed,  and  is 
very  likely  to  contain  crystals  of  acid  urates  or  uric  acid. 
If  such  a  urine  is  allowed  to  stand  a  longer  time,  it  begins 
to  lose  its  acidity  and  finally  becomes  alkaline. 

The  alkalinity  of  the  urine  is  due  either  to  fixed  alkalies, 
— sodium  or  potassium  carbonates, — as  has  already  been 


Plate  2 


Sediment  of  Alkaline   Fermentation  (ai^ter  Hofmann  and 
Ultzmann). 


REACTION.  33 

shown,  or  to  the  product  of  alkahnc  decomposition — 
ammonium  carbonate  formed  from  the  decomposition  of  the 
urea.  When  the  urea  is  acted  upon  by  the  iiira  ferment,  it 
takes  up  two  equivalents  of  water,  and  results  in  ammonium 
carbonate.      Thus  : 

CII,\./)  -f  2H,0  =  (NII,)j,CO,. 

Such  a  urine  has  an  ammoniacal  or  "urinous"  odor, 
giving  off  free  ammonia,  in  contradistinction  to  one  alka- 
hne  from  fixed  alkahes  in  which  no  ammonia  is  evolved. 
A  urine  that  has  undergone  alkaline  decomposition  is 
usually  very  turbid,  partly  from  the  large  number  of 
bacteria  present,  and  partly  from  the  deposit  of  amor- 
phous phosphates  of  calcium  and  magnesium,  and  crystal- 
line elements — notably  ammonio-magnesium  phosphate 
(triple  phosphate),  and  frequently  ammonium  urate.  (See 
Plate  2.)  If  the  urine  is  allowed  to  stand  undisturbed,  its 
surface  may  be  covered  with  a  film,  composed  of  bacteria 
and  a  xegetable  growth,  in  which  crystals  of  ammonio- 
magnesium  phosphate  and  ammonium  urate  are  often  en- 
tangled. Although  this  alkaline  decomposition  is  most 
often  seen  after  the  urine  has  been  allowed  to  stand  in  the 
air  (natural  decomposition),  it  may  be  found  to  have  taken 
place  inside  the  body,  particularly  in  certain  chronic  inflam- 
matory processes  in  the  bladder,  into  which  the  urea  fer- 
ment has  gained  access  ;  the  freshly  passed  urine  then  has 
a  strong  ammoniacal  odor  and  alkaline  reaction. 

Normal  urine  may  have  an  amphoteric  reaction, — /.  e., 
the  same  urine  may  change  blue  litmus  paper  red,  and  red 
litmus  paper  blue, — because  of  the  simultaneous  presence 
in  the  urine  of  variable  proportions  of  acid  and  neutral 
salts. 

Causes  of  Diminished  Acidity. —  i.  After  a  full  meal, 
and  particularly  following  the  ingestion  of  a  vegetable  diet. 
In  vegetarians,  as  in  herbivora,  the  food  contains  an  excess 
of  alkaline  salts  with  vegetable  acids,  such  as  tartaric,  malic, 
citric,  succinic,  etc.  These  acids  are  converted  to  carbon- 
ates, which,  passing  into  the  urine,  give  it  a  neutral  or  alka- 
line reaction. 

2.  Following  the  discharge  of  the  gastric  juice  from  the 
stomach,  as  by  vomiting  or  through  a  gastric  fistula. 

3.  After  the  administration  of  considerable  quantities  of 
alkaline  carbonates,  alkaline  phosphates,  or  caustic  alkalies. 

3 


34  CONSTITUENTS  OF  NORMAL  URINE. 

4.  Decomposition  of  the  urine  (alkaline  fermentation), 
the  urea  being  converted  into  ammonium  carbonate. 

Causes  of  Increased  Acidity. —  i.  Exclusive  meat  diet. 

2.  After  hot  baths  and  free  perspiration. 

3.  Excessive  muscular  exercise  with  free  perspiration. 

4.  Internal  administration  of  acids,  such  as  benzoic  or 
boric  acids. 

5.  The  presence  of  free  fatty  acids  resulting  from  patho- 
logic conditions. 

Specific  Gravity. — The  specific  gravity  of  normal  urine 
is  102 1  for  an  average  amount  of  1500  c.c.  in  the  twenty- 
four  hours.  This  means  that,  taking  distilled  water  at  15.5° 
C.  (60°  F.)  as  I,  each  cubic  centimeter  of  the  urine  weighs 
1.02 1  grams  ;  or  taking  distilled  water  as  looo,  each  cubic 
centimeter  of  the  urine  weighs  1021  grams.  The  specific 
gravity  gives  the  relative  proportion  of  solid  matter  in  the 
urine  ;  then,  by  knowing  the  total  twenty-four-hour  quan- 
tity of  urine,  an  approximate  idea  of  the  absolute  solids  is 
obtained  by  multiplying  the  last  two  figures  of  the  specific 
gravity  by  2.33.  (See  p.  40.)  Under  normal  conditions 
the  specific  gravity  may  vary  between  1018  and  1025,  such  a 
variation  being  dependent  chiefly  upon  the  total  twenty- 
four-hour  amount  of  urine,  the  quantity  and  character  of 
the  food  ingested,  and  the  rapidity  of  tissue  waste.  Thus, 
a  urine  dilute  from  taking  a  large  quantity  of  liquid  may 
have  a  specific  gravity  of  10 18,  or  as  low  as  1012  ;  and,  on 
the  other  hand,  a  concentrated  urine  following  copious  per- 
spiration may  have  a  specific  gravity  of  1025,  or  as  high  as 
1030,  and  be  passed  by  a  perfectly  healthy  individual. 
Such  variations  from  the  normal  are  usually  temporary ; 
if  permanent,  they  are  usually  pathologic.  Nitrogenous 
food,  such  as  meat,  increases  the  solid  matter  in  the  urine, 
and  hence  raises  the  specific  gravity  to  a  greater  or  less 
degree. 

Under  pathologic  conditions  there  is  a  marked  variation 
in  the  specific  gravity,  particularly  in  diseases  of  the  kid- 
neys, but  also  frequently  in  diseases  in  other  parts  of  the 
body  ;  for  example,  in  chronic  interstitial  nephritis  and  in 
diabetes  insipidus  the  specific  gravity  may  be  as  low  as 
1 00 1  or  1002  ;  and,  again,  in  diabetes  mellitus  it  may  go 
as  high  as  1050.  In  most  diseases  of  the  kidney  there 
is  a  tendency  toward  a  low  specific  gravity,  although  it 
may  be  normal  or  even  high.      If  a  normal  or  pale  colored 


SPECIFIC   GRAVITY.  35 

urine  has  a  specific  t^ravity  of  1030  or  more,  the  presence 
of  sugar  is  strongl}'  suggested  ;  but,  on  the  other  hand, 
sugar  may  be  present  with  a  low  specific  gravity  (as  low  as 
10 10) ;  hence  the  importance  of  testing  every  specimen  of 
urine  for  sugar,  regardless  of  the  specific  gravity. 

In  albuminous  urines,  especially  those  containing  one- 
eighth  of  one  per  cent,  or  more,  the  specific  gravity  is  always 
more  or  less  affected  by  the  albumin  in  solution — that  is,  it 
is  raised  higher  than  it  would  be  if  only  normal  urinary 
constituents  were  present. 

The  specific  gravity  of  the  urine  is  also  influenced  by 
certain  drugs  :  for  example,  following  the  administration  of 
large  doses  of  potassium  acetate,  the  specific  gravity  may 
be  1020,  the  total  twenty-four-hour  quantity  increased  to 
2000  c.c.  or  more,  and  the  normal  urinary  constituents  not 
increased.  In  such  a  case  it  is  the  presence  of  the 
increased  amount  of  the  potassium  salts  that  affects  the 
specific  gravit^^ 

The  urinometer  is  undoubtedly  the  most  convenient 
means  of  determining  the  specific  gravity  of  the  urine. 
This  instrument  is  less  accurate  than  the  balance  (Westphal 
or  Mohr)  and  pycnometer,  although  for  practical  purposes 
it  is  sufficiently  accurate  if  it  is  properly  constructed. 
Every  urinometer  should  be  carefully  tested  with  distilled 
water  at  60°  F.  (15.5°  C),  in  which  it  should  read  o  or 
1000.  A  large  number  of  urinometers  are  on  the  market, 
some  .of  which  vary  several  points  from  the  standard,  but 
those  constructed  by  E.  R.  Squibb  &  Sons,  of  Brooklyn, 
New  York,  are  among  the  most  accurate.  (Fig.  i.)  They 
are  very  carefully  standardized  at  "jy^  F.  (25°  C), — a  tem- 
perature much  more  usual  than  60°  F.  (15.5°  C), — and 
with  each  urinometer  a  thermometer  is  furnished  for  tem- 
perature corrections.  In  ordinary  work  the  use  of  the 
thermometer  is  unnecessary,  since  the  variations  by  changes 
in  temperature  are  usually  only  slight  (a  variation  in  the 
reading  of  four  is  the  maximum  error  which  can  occur  at  any 
temperature  at  which  urine  is  likely  to  be  tested — Tyson). 

A  urinometer-glass  should  be  used  whenever  the  specific 
gravity  is  to  be  taken.  Such  a  glass  is  usually  supplied 
with  each  urinometer,  but  the  one  used  by  the  author  (Fig. 
2)  is  strongly  recommended.  ^    This  urinometer-glass  has  the 

'  Manufactured  by  Richard  Briggs  &  Co.,  287  Washington  St.,  Boston. 


36 


CONSTITUENTS  OF  NORMAL  URINE. 


advantage  of  having  a  wide  foot,  perfectly  parallel  sides, 
and  a  well-formed  lip,  not  usually  found  in  the  ordinary 
urinometer-glass.  The  glass  made  by  E.  R.  Squibb  & 
Sons  has  the  added  advantage  of  being  fluted  on  the 
sides. 

In  case  the  specimen  of  urine  is  too  small  for  the  specific 
gravity  to  be  taken  in  the  urinometer-glass  a  sufficiently 
large  test-tube  may  be  used,  but  such  a  tube  should  not  be 
too  small  in  relation  to  the  urinometer ;  nor  should  the 
latter  be  allowed  to  impinge  against  one  side  of  the  glass, 
lest,  in  consequence  of  the  capillary  attraction  between  the 


Fig.  I. — Squibb's  urinometer. 


Fig.  2.— Urinometer   and    urinometer-glass 
(slightly  smaller  than  one-half  actual  size). 


tube  and  the  urinometer,  the  latter  should  not  sink  to  the 
proper  level.  The  urinometer  should  be  introduced  into 
the  tube  containing  the  urine,  allowed  to  find  its  proper 
level,  and  the  reading  taken;  the  urinometer  should  then 
be  forced  down  into  the  urine,  allowed  to  rise  until  it  again 
reaches  its  proper  level,  and  a  second  reading  taken.  The 
two  readings  should  be  exactly  the  same.  Any  discrepancy 
in  the  readings  shows  that  in  either  one  or  the  other  obser- 
vation the  urinometer  impinged  against  one  side  of  the 
tube,  from  which  it  is  readily  freed  by  moving  it  gently  from 
side  to  side. 


SPECIFIC  GRAVITY.  37 

Method  of  Taking  Specific  Gravity  by  the  Urinome- 
ter. — Fill  the  urinometer-glass  three-fourths  full  of  urine  ; 
introduce  the  urinomcter,  pushing  it  down  into  the  urine  so 
that  it  just  touches  the  bottom  of  the  urinometer-glass, 
then  release  it  and  wait  until  it  finds  the  correct  level ;  when 
it  comes  to  a  rest,  the  scale  is  read  off  through  the  fluid 
from  below  upward,  the  last  mark  seen  below  the  surface 
(at  the  meniscus)  being  the  correct  specific  gravity.  The 
reading  should  )iot  be  taken  from  above  the  surface  of  the 
fluid,  since  the  capillary  attraction  of  the  fluid  on  the  shaft 
of  the  urinometer  causes  an  error  of  from  one  to  two  grad- 
uations on  the  scale. 

If  the  quantity  of  urine  is  too  small  to  fill  sufficiently  the 
cylinder,  it  may  be  diluted  with  enough  distilled  water  to 
fill  the  cylinder  to  the  required  height,  noting  the  volume 
added.  From  the  specific  gravity  of  this  mixture  may  be 
calculated  that  of  the  urine.  Thus,  suppose  it  is  necessary 
to  add  four  times  as  much  water  as  urine  to  enable  us  to 
use  the  urinometer — that  is,  to  make  five  volumes — and 
the  specific  gravity  of  the  mixed  fluid  is  1004,  then  that  of 
the  urine  will  be  looo  +  (4x5)=  1020.  Although  the 
principle  of  this  method  is  correct, — and  the  results  must 
be  if  the  data  are, — the  urinometers  in  use  are  not  usually 
so  finely  graduated  that  absolute  accuracy  in  reading  is 
secured,  while  any  error  in  reading  is  multiplied  by  the 
number  of  volumes  used.  Hence,  it  is  desirable  to  use  this 
method  as  rarely  as  possible,  especially  with  urine  of  low 
specific  gravity. 

Solids. — The  term  "solids,"  as  ordinarily  applied,  refers 
to  the  normal  constituents  of  the  urine  present  in  solution, 
such  as  urea,  chlorides,  uric  acid,  phosphates,  sulphates, 
ethereal  sulphates,  and  various  other  constituents  present 
in  smaller  quantities. 

"  Relative  "  and  "  Absolute  "  Solids. — The  term  rela- 
tivc  solids  applies  to  the  proportion  of  solid  matter  to  that 
of  the  water  which  contains  it :  for  example,  the  relative 
quantity  of  urea  is  normally  tzvo  per  cent. — that  is,  two 
parts  of  urea  in  one  hundred  parts  of  urine.  The  absolute 
solids  are  the  solids  contained  in  the  total  twenty-four-hour 
urine,  calculated  in  grams  or  grains :  for  example,  the 
absolute  quantity  of  urea  is  normally  thirty-three  grams — 
that  is,  the  total  quantity  of  urea  in  twenty-four  hours. 

The  specific  gravity  of  the  urine  affords  a  general  idea  of 


38  CONSTITUENTS  OF  NORMAL  URINE. 

the  total  solids  present,  but  that  in  itself  is  not  sufficient. 
It  is  therefore  necessary,  first,  to  obtain  the  relative  propor- 
tion of  the  most  important  constituents, — as  Tjrea,  chlorides, 
phosphates,  sulphates,  uric  acid,  etc., — and,  second,  to  de- 
termine the  absolute  quantities  of  these  solids,  before  infer- 
ences can  be  deduced  therefrom.  Observations  concerning 
the  solids  of  the  urine  should  be  made  upon  a  sample  of 
the  mixed  twenty-four-hour  secretion,  and  not  on  the  urine 
of  a  single  micturition. 

Under  normal  conditions  the  total  solids  amount  to  from 
seventy  to  seventy-three  grams  in  twenty-four  hours,  of 
which  urea  constitutes  nearly  one-half,  the  chlorides  about 
one-fifth,  and  the  phosphates  about  one-twenty-fifth.  The 
absolute  quantity  of  urea,  being  the  most  abundant  solid 
of  the  urine,  is  of  the  greatest  importance  in  judging  of  the 
capability  of  the  kidneys  for  work,  and  also  the  extent  of 
tissue  metabolism  in  both  health  and  disease.  The  abso- 
lute quantities  of  chlorine  and  phosphoric  acid  are  also 
important  in  some  cases  in  completing  the  picture  of  the 
urine. 

The  actual  quantity  of  solids  in  the  urine,  particularly 
the  total  quantities  of  each  of  the  most  important  constitu- 
ents, having  been  ascertained,  in  order  to  make  valuable 
deductions  therefrom  in  health  or  disease  it  is  necessary  to 
take  into  consideration  the  weight,  age,  habits,  diet,  sur- 
roundings, and  the  nature  of  the  disease  in  each  individual 
case  before  deciding  as  to  the  extent  of  the  increase  or 
diminution  of  the  solids  for  a  given  individual.  For  ex- 
ample, on  an  average  mixed  diet,  a  large  adult  male  nor- 
mally excretes  a  larger  quantity  of  solids  than  a  small  adult 
male  (the  average  for  a  person  of  66  kilograms  being 
from  66  to  75  grams,  of  which  urea  equals  from  35 
to  40  grams)  ;  and  a  large  adult  female,  a  larger  quantity 
than  a  small  adult  female  (the  average  for  a  person  of  55 
kilograms  being  from  60  to  jo  grams,  of  which  urea 
equals  from  25  to  35  grams).  In  persons  between  fifty  and 
seventy  years  of  age  the  total  solids  fall  materially  in  health. 
In  healthy  children,  although  the  total  solids  are  far  below 
the  average  for  an  adult,  they  are  larger  in  proportion  to 
the  height,  age,  and  weight  than  in  the  adult.  Much  de- 
pends also  on  the  diet — that  is,  a  person  ingesting  an 
abundance  of  nitrogenous  food  will  excrete  larger  quanti- 
ties of  solids,  especiall}'  urea.      On  the  other  hand,  when  a 


TOTAL  SOLIDS.  3i) 

meager  diet,  or  one  consisting  chiefly  of  milk,  is  takcMi,  the 
soHds  arc  usually  diminished. 

In  most  chronic  diseased  conditions  the  solids  are  more  or 
less  diminished,  whether  the  disease  be  in  the  kidneys  or  in 
some  other  organ  or  organs  of  the  body,  and  particularly 
when  the  patient  is  not  capable  of  taking  or  assimilating  a 
mixed  diet.  The  total  solids  are  notably  diminished  in  ad- 
vanced chronic  diseases  of  the  kidney,  in  which  the  functions 
of  these  organs  are  greatly  interfered  with  on  account  of  the 
diseased  epithelium  lining  the  renal  tubules.  A  marked 
reduction  of  the  solids  in  renal  disease  often  indicates  a 
tendency  to  uremia,  although  this  dangerous  complication 
may  arise  when  the  solids  are  normal  or  only  slightly  dimin- 
ished. In  the  early  stages  of  acute  fevers  the  solids  may, 
for  a  short  period,  be  normal  or  increased,  but  usually  at 
the  expense  of  the  tissues  (increased  metabolism),  whereas, 
later,  they  are  markedly  diminished.  During  the  conva- 
lescence, however,  they  usually  reach  the  normal,  or  are 
increased.  In  diabetes  mellitus  and  insipidus  the  total 
solids  (aside  from  the  sugar  in  the  former  disease)  are  gen- 
erally increased. 

Determination  of  Total  Solids. — The  total  solids  of  the 
urine  may  be  determined  in  the  following  ways  : 

1.  Take  five  cubic  centimeters  of  the  mixed  twenty-four- 
hour  urine  in  a  previously  dried  and  weighed  platinum  or 
porcelain  dish.  Evaporate  it  in  a  vacuum  over  sulphuric  acid. 
After  twenty-four  hours  remove  this  sulphuric  acid  and  re- 
place by  fresh  acid  ;  exhaust  again,  and  weigh  after  an- 
other twenty-four  hours.  Deduct  the  weight  of  the  dish, 
and  the  remainder  gives  the  solids  in  five  cubic  centimeters 
of"  urine.  From  this  the  solids  in  the  whole  volume  of 
urine  are  readily  calculated.  This  method  is  one  of  the 
most  accurate  for  the  determination  of  the  solids  of  the 
urine. 

2.  A  quicker  method  is  to  evaporate  to  dryness  over  a 
water-bath  a  given  quantity  of  urine — say  twenty-five  cubic 
centimeters — in  a  previously  dried  and  weighed  porcelain 
dish.  Dry  the  residue  by  placing  the  dish  in  an  oven  at  i  io° 
C.  (230°  F.)  for  a  few  hours  ;  cool  and  weigh.  This  should 
be  repeated  several  times  until  no  further  loss  of  weight 
occurs  from  drying.  Subtract  the  weight  of  the  dish,  and 
the  remainder  will  represent  the  solids  in  twenty-five  cubic 
centimeters  of  the   urine.      This  method,   however,    is   not 


40  CONSTITUENTS  OF  NORMAL  URINE. 

very  accurate,  as  some  of  the  compounds  in  the  urine  are  de- 
composed at  a  temperature  of  iio°  C.  (230°  F.). 

J.  To  Determine  the  Solids  in  the  Tiventy-fotir-hour  Urine 
by  Means  of  the  Specific  Gravity. — Knowing  the  quantity  of 
urine  passed  in  twenty-four  hours  and  its  specific  gravity,  an 
approximate  estimation  of  the  total  quantity  of  sohd  matter 
may  be  readily  obtained  by  multiplying  the  last  two  figures 
of  the  specific  gravity  by  the  arbitrary  coefficient  of 
Haeser,  2.33.  This  will  give  the  approximate  number  of 
grams  of  solids  in  1000  c.c.  of  the  urine.  For  example, 
suppose  the  twenty-four-hour  urine  to  be  1350  c.c,  and 
the  specific  gravity  to  be  1024,  then 

24  X  2.33  =  55.92  grams  in  looo  c.c. 

Since  the  total  quantity  of  urine  in  twenty-four  hours  is 
1350  c.c,  it  will  contain 

55.92  X  1350 

1000  :  1350  :  :  55.92  :  x,  =  ^^^ =  75.49 

grams  in  twenty -four  hours.  This  result  indicates  that  a 
trifle  more  than  the  average  normal  quantity  of  solids  has 
been  excreted. 

While  this  method  of  arriving  at  the  quantity  of  solids  is 
not  sufficiently  accurate  for  scientific  purposes,  it  is  often  of 
considerable  value  for  clinical  purposes.  It  should  be  borne 
in  mind,  however,  that  if  the  urine  contains  solid  matter  other 
than  the  normal  constituents,  the  solids  obtained  by  this 
method  will  often  be  found  to  be  very  high.  For  example, 
in  case  of  diabetes  mellitus  they  will  be  found  to  be  above 
the  normal,  due  to  the  presence  of  the  sugar  ;  highly 
albuminous  urines  may  have  increased  total  solids,  due  to 
the  quantity  of  albumin  present.  So  also,  after  the  use  of 
certain  drugs,  such  as  the  potassium  salts, — viz.,  acetate, 
citrate,  bitartrate,  etc., — the  solids  will  be  considerably 
above  the  normal,  because  of  the  presence  of  these  salts. 


CHAPTER  II. 
ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

UREA. 
CH4N0O. 

Urea  is  the  chief  organic  constituent  of  the  urine.  It  is 
isomeric  with  ammonium  cyanate,  from  which  it  was  first 
prepared  synthetically  by  Wohler.  It  may  also  be  prepared 
by  the  action  of  ammonia  on  carbonyl  chloride,  by  hydra- 
tion of  cyanamide,  and  from  ammonium  carbonate. 

Urea  is  readily  soluble  in  alcohol  and  water,  but  insoluble 
in  ether.  It  is  odorless,  has  a  salty  taste,  and  its  solution 
has  a  neutral  reaction.  Urea  crystallizes  in  colorless  four- 
or  six-sided  prisms  with  oblique  ends,  or,  when  rapidly  crys- 
tallized, in  delicate,  white,  silky  needles.  When  treated 
with  nitric  acid,  nitrate  of  urea — C0N,H^,HN03 — is  formed, 
which  crystallizes  in  octahedral,  hexagonal,  or  lozenge- 
shaped  plates.  These  plates  are  usually  arranged  in  strata, 
although  occasionally  seen  singly  (Fig.  3),  and  are  less 
soluble  in  water  than  urea  crystals.  With  oxalic  acid  urea 
unites  to  form  oxalate  of  urea, — (CON^H^)^,  H2C20^  +  H^O, 
— which  is  in  the  form  of  flat  or  prismatic  crystals. 

Other  compounds  of  urea  with  acids  have  also  been  de- 
scribed ;  thus,  phosphate  of  urea,  CON^H^,  HgPO^,  was 
said  by  Lehmann  ^  to  occur  in  small  quantities  in  urine  ;  a 
compound  of  urea  with  uronitrotoluolic  acid — with  the 
formula  C,^Hj,,N.^O,„ — was  found  by  Jaffe  ^  in  dogs'  urine 
after  the  administration  of  orthonitrotoluol  ;  the  greater 
part  of  the  urea  in  urine  is,  however,  free. 

Urea  also  forms  compounds  with  salts,  the  most  impor- 
tant being  with  mercuric  nitrate.  With  this  substance  it 
forms  a  white  precipitate  having  the  formula  CON„H^ .  Hg- 
(NO3).,  .  3HgO.      This  compound  is  important,  as  Liebig's 

1  "  Cheinische  Centralblatt,"   1866,  S.  1119. 

2  "  Zeitschrift  fur  physiologische  Chemie,"  II,  50. 

41 


42  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

volumetric   process  for  the  estimation  of  urea  is  based  on 
its  formation. 

There  is  also  a  crystalline  compound  of  urea  with  sodium 
chloride,  CON2H^ .  NaCl  +  H2O,  which  may  be  obtained 
by  evaporating  to  dryness  a  solution  of  these  two  sub- 
stances, such  as  occurs,  for  instance,  in  ordinary  urine. 
Urea  may  be  decomposed  in  various  ways  : 
I.  When  heated  to  from  150°  to  170°  C,  it  melts  and 
gives  off  ammonia  ;  the  substance  which  remains  is  termed 

biuret.  1 

2CON.,H^  —  NH3  =  Cp.NjHj. 
Urea.  Biuret. 

Biuret  with  caustic  potash  and  copper  sulphate  gives  a 


Fig,  3.— Crystals  of   nitrate  of  urea  (upper  half)  and  oxalate  of   urea    (lower  half) 

(after  Funke). 


characteristic  rose-red  solution.      When  biuret  is  heated,  it 
gives  off  ammonia,  and  cyanuric  acid  is  left — 

3C.,0,,N3H,  -  3NH3  =  2C3H3N3O,. 

Biuret.  Cyanuric  acid. 

Cyanuric  acid  gives  a  violet  solution  with  caustic  potash 
and  copper  sulphate. 

2.  By  means  of  an  organized  ferment,  the  torula,  or  micro- 
coccus ureae  (which  grows  readily  in  stale  urine),  urea  takes 
up  water,  and  is  converted  into  ammonium  carbonate — 
CON^H,  +  2H,0  =  (NHJ.COg. 

1  "Poggendorfs  Annalen,"  Lxxiv,  67. 


UREA.  43 

3.  By  means  of  nitrous  acid  urea  is  broken  up  into  car- 
bonic acid,  water,  and  nitrogen — CON,H^  ~\-  N,03  =  CO2 
-f  2H2O  +  2N,. 

4.  Chlorine  water  causes  a  somewhat  similar  decomposi- 
tion—COK,H,   +    HP   +    3CI,  -=   CO2  +  N^  +  6HC1. 

5.  Hypochlorite  or  hypobromite  of  soda  decomposes 
urea  in  the  following  way  :  CON2H^  -f  3NaOBr  =  CO, 
-f-  Ng  -|-2H.,0  +  3NaBr.  This  reaction  is  important,  as 
upon  it  is  based  one  of  the  best  methods  of  estimating  the 
quantity  of  urea  in  urine.      (See  p.  50.) 

Since  urea  is  the  chief  organic  constituent  of  the  urine, 
it  is  a  fair  index  of  the  excretion  of  nitrogenous  matter  from 
the  body.  Not  all  of  the  nitrogen,  however,  is  excreted  as 
urea,  as  very  small  amounts  of  it  go  out  as  uric  acid, 
xanthin,  hypoxanthin,  sarkin,  kreatinin,  allantoin,  etc. 

Much  discussion  has  arisen  in  the  past  in  relation  to  the 
formation  of  urea — especially  where  it  is  formed  and  from 
what  it  is  formed.  As  first  pointed  out  by  Meissner,i  urea 
is  probably  formed  chiefly  in  the  liver.  This  view  has 
been  confirmed  by  the  more  recent  experiments  of  Brou- 
ardel,2  Roster,^  Schroeder,^  and  Minkowski.^  It  is  also 
probable  that  the  spleen  and  lymphatic  and  secreting  glands 
participate  in  the  formation  of  urea.  The  urea  passes  into 
the  blood,  and  is  carried  to  the  kidneys,  where  it  is  excreted. 
Contrary  to  the  early  belief,  urea  is  not  formed  in  the  kid- 
neys, or,  if  at  all,  only  in  minute  quantities,  as  was  first 
demonstrated  by  Prevost  and  Dumas, ^  who  found  that  the 
formation  of  urea  continued,  accumulating  in  the  blood  and 
tissues,  even  after  the  complete  extirpation  of  the  kidneys. 
Similarly,  in  extensive  disease  of  the  kidneys  in  which 
there  is  almost  complete  suppression  of  urine,  urea  con- 
tinues to  be  formed  and  collects  in  the  organism.  Further- 
more, in  support  of  this  view  w^e  find  that  in  extensive  de- 
generative changes  in  the  liver,  as  in  acute  yellow  atrophy, 
the  formation  of  urea  is  greatly  diminished.  On  the  other 
hand,  in  those  diseases  of  the  liver  in  which  the  activity  of 
the  liver-cells  is  greatly  increased,  as  in  diabetes  mellitus, 
the  urea  formation  is  increased. 

1  "Zeit.  f.  rat.  Med.,"  N.  F.,  xxxi,  234. 

2  "  Archiv  de  physiol.  norm,  et  pathol.,"  [2]  III,  373,  551. 

3  Quoted  by  Hoppe-Seyler,  "  Physiol.  Chem. ,"  S.  807. 
*  "Lud wig's  Festschrift,"  1887,  .S.  89. 

5  "Ann.  de  Chim.  et  de  Physiol.,"  xxiii,  90. 


44  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

The  quantity  of  urea  eliminated  in  twenty-four  hours 
varies  considerably,  the  chief  cause  of  variation  being  the 
amount  of  proteid  food  ingested,  together  with  the  rapidity 
of  tissue  metabolism  in  health  or  disease.  In  a  man  who 
is  in  a  state  of  equilibrium,  and  on  an  ordinary  mixed  diet, 
the  quantity  of  urea  excreted  daily  is  between  25  and  40 
grams,  the  average  being  about  33  grams  (500  grains).  On 
a  diet  poor  in  nitrogenous  matter  it  may  fall  to  from  1 5  to 
20  grams  ;  and,  on  the  other  hand,  on  a  diet  rich  in  nitrogen 
it  may  rise  to  from  60  to  80  grams  per  diem.  The  per- 
centage of  urea  varies  considerably  ;  it  may  be  roughly 
said  that  the  average  relative  quantity  in  health  is  two  per 
cent.  ;  but  the  percentage  usually  varies  with  the  concentra- 
tion of  the  urine. 

Women  excrete  rather  less  urea  than  men  ;  children  less, 
absolutely,  than  adults,  but  more  in  proportion  to  their 
weight.  Uhle  gives  the  following  table,  which  represents 
the  quantity  of  urea  excreted  in  twenty -four  hours  per  kilo- 
gram of  body-ivcigJit  at  different  ages  : 

From  3-6    years, about  I  gram. 

"     8-11'  " "0.8 

"   13-16     "      "     0.4-0.6      " 

Adults, "     0.37-0.6    " 

From  this  it  is  seen  that,  per  kilogram  weight,  children  up 
to  eleven  years  of  age  excrete  about  twice  the  quantity  of 
urea  that  adults  do,  and  after  eleven  years  practically  the 
saine  as  adults. 

An  Increased  Quantity  of  Urea. — (a)  In  health  the 
absolute  quantity  of  Jitea  may  be  increased  by__^i)_^5__ 
hearty  mixed  diet.  \2)  ^trenuous  exeTcrsc  causing  in- 
creased metabolism  ;  and-it  is  for  this  reason  that  the  quan- 
tity of  urea  is  greater  during  the  day  than  during  the  night : 
the  average  proportion,  ,of  the  day  to  the  night  urea  being 
as  three  is  to  two.  1(3)  \y  the  ingestion  of  ammonium 
compounds,  particularly  ammonium  chloride,  it  having  been 
found  that  practically  nine-tenths  of  the  mfacQgen  in  the 
ammonium  chloride  is  eliminated  as  urea.  i(4)\By  the  in- 
gestion of  large  quantities  of  water,  the  metkbblism  being 
increased  thereby,  especially  when  an  abundance  of  water  is 
taken  for  a  short  time.  If  this  ingestion  is  continued  for  a 
long  time,  the  metabolism  is  diminished,  and  hence  there  is 
a  diminution  in  the  urea.  if5)NFollowing  hot  baths  the  urea 
may  be  increased. 


UREA.  45 

(b)  In  disease  the  absolute  quantity  of  urea  is  in- 
creased (i)  in  the  early  stages  of  acute  febrile  diseases,  the 
increase  being  due  largely  to  the  increased  metabolism  of 
the  tissues,  which,  together  with  the  ingestion  of  very  little 
food,  results  in  emaciation.  One  notable  exception  to  this, 
however,  is  in  acute  diseases  associated  with  increasing 
dropsy,  as  in  acute  nephritis  ;  also  those  accompanied  by 
exudations  into  other  parts  of  the  body,  as  in  cholera  ;  and 
other  acute  intestinal  diseases  in  which  there  is  marked 
diarrhea.  (2)  During  the  convalescence  from  acute  dis- 
eases associated  with  dropsy  the  urea  may  be  increased 
during  the  time  that  the  dropsical  fluid  is  being  reabsorbed. 
Such  an  increase,  however,  is  usually  only  temporary, 
and  after  all  of  the  dropsical  fluid  has  been  absorbed  the 
urea  falls  below  the  normal,  as  is  the  rule  in  convalescence 
from  other  acute  diseases.  (3)  In  intermittent  fever  the 
urea  is  increased  before  the  patient  has  a  chill,  but  dimin- 
ished afterward.  (4)  In  diabetes  insipidus  the  urea  is  much 
increased  absolutely  (may  go  as  high  as  130  grams),  the 
twenty-four-hour  quantity  of  urine  being  very  large,  but 
the  specific  gravity  very  low.  (5)  In  diabetes  mellitus,  on 
account  of  the  increased  metabolism,  the  total  urea  is 
usually  above  the  normal.  (6)  In  chronic  interstitial  neph- 
ritis, although  the  absolute  quantity  of  urea  is  usually 
diminished,  it  may,  in  rare  instances,  be  absolutely  in- 
creased. This  has  been  occasionally  observed  in  children 
by  the  writer,  where,  at  the  autopsy,  the  disease  was  found 
to  exist  to  a  marked  degree.  (7)  In  chronic  gout  the  urea 
may  be  increased  to  fifty  or  sixty  grams  in  twenty-four 
hours. 

A  Diminished  Quantity  of  Urea. — (a)  In  health  the^. 
urea  is  diminished  absolutely  (i)  whenever  very  little  nitro- 
genous food  is  taken — seen  especially  in  vegetarians  ;  also 
in  those  instances  in  which  the  individual  takes  very  little 
food  of  any  kind.  (2)  Sometimes,  following  very  free  per- 
spiration, the  urea  is  diminished  absolutely  on  account  of 
the  elimination  of  a  certain  amount  of  this  substance  by 
the  sweat-glands.  (3)  In  many  instances  of  normal  preg- 
nancy the  total  urea  is  diminished.  This  is  explained  on 
the  ground  that  the  nitrogenous  elements  ingested  go  to 
nourish  the  fetus.  The  average  amount  of  urea  in  normal 
pregnancy  is  about  twenty  grams  in  twenty-four  hours. 
(4)  Following  the  administration  of  small  doses  of  quinine 


46  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

(Oppenheim)  the  urea  is  low,  although  not  markedly  dimin- 
ished. (5)  The  long-continued  ingestion  of  excessive 
quantities  of  water  results  in  more  or  less  reduction  in  the 
total  quantity  of  urea. 

(b)  In  disease  the  urea  is  generally  diminished,  the  ex- 
tent of  the  diminution  being  usually  dependent  upon,  first, 
the  degree  of  diminished  metabolism,  and,  second,  the  capa- 
bility of  the  kidneys  to  excrete  the  urea,  (i)  In  most  diseases 
of  the  kidneys — especially  the  advanced  chronic  forms,  such 
as  chronic  interstitial,  chronic  diffuse,  and  subacute  glomer- 
ular nephritis — the  urea  is  usually  markedly  diminished. 
In  amyloid  infiltration  it  may  be  normal  or  diminished,  but 
usually  not  so  much  diminished  as  in  chronic  interstitial 
nephritis,  since  in  the  former  disease  the  infiltration  takes 
place  about  the  blood-vessels,  and  consequently  does  not 
interfere  with  the  secreting  structure  of  the  kidney  until  very 
late.  On  the  other  hand,  in  chronic  interstitial  nephritis  the 
secreting  portion  of  the  kidney  is  affected  much  earlier  in 
the  disease.  Not  infrequently  a  determination  of  the  abso- 
lute amount  of  urea  is  of  considerable  aid  in  the  differential 
diagnosis  of  these  two  forms  of  Bright' s  disease.  In  the 
first  two  stages  of  acute  nephritis  the  urea,  absolutely,  is 
much  below  the  normal,  especially  in  the  first  stage  or  at 
the  time  when  the  dropsy  is  increasing.  (2)  In  the  func- 
tional disturbances  of  the  kidneys — active  and  passive 
hyperemias — the  urea  is  frequently  diminished,  the  extent 
of  the  diminution  being  largely  dependent  upon  the  cause 
of  the  disturbance.  (3)  In  acute  febrile  diseases  following 
the  acme  of  the  disease  the  quantity  of  urea  is  low,  and 
likewise  during  the  convalescence  from  these  diseases,  since 
the  nitrogenous  elements  go  to  build  up  the  tissues.  (4)  In 
all  diseases  attended  with  extensive  dropsy  the  urea  is  dimin- 
ished up  to  the  time  the  effusion  begins  to  be  reabsorbed, 
when  it  gradually  increases.  (5)  Shortly  before  death  from 
any  cause  the  urea  is  usually  markedly  diminished  (five  to 
six  grams  in  twenty-four  hours),  more  especially  in  chronic 
kidney  diseases.  In  those  cases  in  which  the  degeneration 
of  the  renal  tissue  is  very  extensive  and  the  kidneys  are 
not  capable  of  excreting  the  urea,  the  elimination  may 
take  place  through  other  glands,  notably  the  sweat-glands. 
In  such  instances  the  skin,  especially  in  the  axillae  and 
groins,  has  been  found  to  be  covered  with  a  coating  of 
crystallized  urea.      (6)   Extensive  vomiting,  and  (7)  marked 


DETFXTION   OF   UREA.  47 

cases  of  diarrhea  cause  a  diminution  in  the  amount  of  the 
urea  eHminated  ;  this  is  particularly  true  in  connection  with 
extensive  renal  disease,  a  portion  of  the  urea  being  elim- 
inated by  these  channels.  (8)  In  all  degenerative  changes  in 
the  liver,  as  in  acute  yellow  atrophy,  there  is  very  low  urea, 
it  apparently  being  replaced  by  leucin  and  tyrosin. 

Detection. — The  presence  of  urea  may  be  detected  in 
the  following  ways  : 

1.  Place  a  drop  of  the  urine  on  a  watch-glass  or  glass 
slide,  add  one  drop  of  pure  nitric  acid  (the  yellow  nitric 
acid  should  be  avoided),  and  allow  the  mixture  to  evapo- 
rate spontaneously  in  the  air.  If  urea  be  present,  crystals 
of  nitrate  of  urea  will  be  seen  when  examined  with  the 
microscope. 

2.  To  a  drop  of  the  urine  add  a  drop  of  a  saturated  solu- 
tion of  oxalic  acid.  If  urea  be  present,  crystals  of  oxalate 
of  urea  form,  which,  under  the  microscope,  appear  in  the 
form  of  rhombic  plates,  or  short,  thick,  rhombic  prisms. 

3.  To  the  urine  add  an  equal  volume  of  sodium  hypo- 
bromite  or  hypochlorite,  and  if  urea  be  present,  the  evolu- 
tion of  nitrogen  gas  takes  place. 

4.  Place  a  few  crystals  of  urea  in  a  test-tube,  and  heat  to 
melting;  then  add  a  few  drops  of  sodium  or  potassium 
hydrate  and  a  drop  or  two  of  a  dilute  solution  of  sulphate 
of  copper.  The  biuret  reaction  occurs,  which  consists  of  a 
violet  or  a  rose-red  color. 

5.  To  a  crystal  of  urea  about  the  size  of  the  head  of  a 
pin  add  one  drop  of  a  moderately  concentrated  solution 
of  furfurol,  and  then  a  drop  of  concentrated  hydrochloric 
acid,  and  heat.  A  play  of  colors  results  :  a  yellow,  green, 
blue,  violet,  and,  finally,  in  the  course  of  a  few  minutes,  a 
purple-violet  (furfurol  reaction  of  Schiff  i). 

Quantitative  Determination  of  Urea.  —  Various  \ 
methods  have  been  suggested  for  the  quantitative  determina- 
tion of  urea.  Of  these,  the  three  following  are  most  suit- 
able :  (rt)  The  mercuric  nitrate  or  Liebig's  method  ;  {/>) 
the  hypobromite  or  hypochlorite  method ;  (r)  Fowler's 
hypochlorite  method  (differential  density). 

(a)   Liebig's  Method. — If  albumin  be  present,  it  must  first  ^ 
be  removed  by  coagulation  (heat).     The  combination  between 
urea  and  mercuric  oxide,  which  is  (CON2Hj2Hg(N03)2 .  3HgO, 

1  "  Berichte  d.  chem.  Gesellsch.,"  x,  773,  1887. 


48  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

results  in  a  white  precipitate,  insoluble  in  water  and  weak 
alkaline  solutions.  It  is,  therefore,  necessary  to  prepare  a 
standard  solution  of  mercury,  and  to  have  an  indicator  by  which 
to  detect  the  point  when  all  the  urea  has  entered  into  combina- 
tion with  the  mercury,  and  the  latter  slightly  predominates. 
This  indicator  is  sodium  carbonate,  which  gives  a  yellow  color 
with  the  excess  of  mercury,  owing  to  the  formation  of  hydrated 
mercuric  oxide. 

Theoretically,  loo  parts  of  urea  should  require  720  parts  of 
mercuric  oxide;  but  practically,  772  of  the  latter  are  necessary 
to  remove  all  the  urea,  and  at  the  same  time  show  the  yellow 
color  with  alkali;  consequently,  the  solution  of  mercuric  nitrate 
must  be  of  empiric  strength  in  order  to  give  accurate  results. 

The  following  solutions  must  be  prepared  : 

1.  Standard  Mercuric  Nitrate  Solution:  Dissolve  77.2  grams 
of  red  oxide  of  mercury  (weighed  after  it  has  been  dried  over 
a  water-bath),  or  71.5  grams  of  the  metal  itself,  in  dilute  nitric 
acid.  Expel  the  excess  of  acid  by  evaporating  the  liquid  to  a 
syrupy  consistence.  Make  up  to  1000  c.c.  with  distilled  water, 
adding  the  water  gradually.  This  solution  is  of  such  strength 
that  19  c.c.  will  precipitate  10  c.c.  of  a  2  per  cent,  urea  solu- 
tion. Add  52.6  c.c.  of  water  to  the  liter  of  the  mercuric  nitrate 
solution,  and  shake  well ;  then  20  c.c.  (instead  of  19)  =  10  c.c. 
2  per  cent,  urea  solution — /.  ^. ,  i  c.c.  =  o.oi  of  urea. 

2.  Baryta  Mixture:  This  is  a  mixture  of  two  volumes  of 
solution  of  barium  hydrate  with  one  of  solution  of  barium 
nitrate,  both  saturated  in  the  cold. 

Analysis. — Take  40  c.c.  urine;  add  to  this  20  c.c.  of  baryta 
mixture,  and  filter  off  the  precipitate  of  baryta  salts  (phosphates 
and  sulphates);  take  15  c.c.  of  the  filtrate  (this  corresponds  to 
10  c.c.  of  urine)  in  a  beaker.  Run  into  it  the  mercuric  nitrate 
solution  from  a  burette,  until,  on  mixing  a  drop  of  the  mixture 
with  a  drop  of  a  saturated  solution  of  sodium  carbonate  on  a 
white  tile,  a  pale  lemon  color  appears.  Then  read  from  the 
burette  the  amount  used,  and  calculate  from  this  the  percentage 
of  urea. 

Corrections. — This  method  approaches  accuracy  only  when 
the  quantity  of  urea  present  is  about  2  per  cent.,  which  is  about 
the  normal  percentage  of  urea  in  urine.  The  chlorine  in  the 
urine  must  also  be  estimated,  and  the  quantity  of  urea  indicated 
reduced  by  the  subtraction  of  i  gram  of  urea  for  every  1.3 
grams  of  sodium  chloride  found.  If  the  urine  contains  less 
than  2  per  cent,  of  urea,  o.i  c.c.  of  mercuric  nitrate  solution 
must  be  deducted  for  every  4  c.c.  used;  if  more  than  2  per 
cent,  of  urea,  a  second  titration  must  be  performed  with  the 
urine  diluted  with  half  as  much  water  as  has  been  needed  of 
the  mercurial  solution  above   20  c.c.     Suppose,  then,  28  c.c. 


QUANTITATIVE  DETERMINATION   OF   UREA.  49 

have  been  used  in  the  first  titration,  the  excess  is  8  c.c;  there- 
fore 4  c.c.  of  water  must  be  added  to  the  urine  before  the 
second  titration  is  made.  When  ammonium  carbonate  is  present, 
first  estimate  the  urea  in  one  portion  of  urine,  and  the  ammonia 
by  titration  with  normal  sulphuric  acid  in  another;  0.017  gram 
of  ammonia  =  0.030  of  urea.  The  equivalent  of  ammonia  in 
terms  of  urea  must  be  added  to  the  urea  found  in  the  first 
portion  of  urine. 

Modifications. — Rautenberg  and  Pfliiger  have  devised  modifi- 
cations of  Liebig's  original  method.  Rautenberg's  method 
consists  in  maintaining  the  urea  solution  neutral  throughout  by 
successive  additions  of  calcium  carbonate.  Pfluger's  method  is 
as  follows:  A  2  per  cent,  solution  of  urea  is  prepared  ;  10  c.c. 
of  this  are  placed  in  a  beaker,  and  20  c.c.  of  the  mercuric  nitrate 
solution  are  run  into  it  in  a  continuous  stream  ;  the  mixture  is 
then  brought  under  a  burette  containing  normal  sodium  car- 
bonate, and  this  is  added  with  constant  agitation  until  a  per- 
manent yellow  color  appears.  The  volume  so  used  is  noted  as 
that  necessary  to  neutralize  the  acidity  produced  by  20  c.c.  of 
the  mercurial  solution  in  the  presence  of  urea.  A  plate  of  glass 
is  then  laid  on  a  black  cloth,  and  some  drops  of  a  strong  solu- 
tion of  sodium  bicarbonate  (free  from  carbonate)  are  placed 
upon  it  at  convenient  distances.  The  mercurial  solution  is 
added  to  the  urine  in  such  volume  as  is  judged  appropriate,  and 
from  time  to  time  a  drop  of  the  white  mixture  is  placed  beside 
the  bicarbonate,  so  as  to  touch  but  not  mix  completely.  A 
point  is  at  last  reached  when  the  white  gives  place  to  yellow ; 
both  drops  are  then  quickly  mixed  with  a  glass  rod,  and  the 
color  disappears ;  further  addition  of  mercury  is  then  made  to 
the  urine  until  a  drop  mixed  with  the  bicarbonate  remains  per- 
manently yellow.  Now  is  the  time  to  neutralize  by  the  addition 
of  the  normal  sodium  carbonate  to  near  the  volume  found  neces- 
sary in  the  preliminary  experiment.  If  this  is  quickly  done,  a 
few'  tenths  of  a  cubic  centimeter  of  mercuric  nitrate  will  be 
found  sufficient  to  complete  the  reaction.  If,  however,  much 
time  has  been  lost,  it  may  happen  that,  notwithstanding  the 
mixture  is  distinctly  acid,  it  gives,  even  after  the  addition  of 
sodium  carbonate,  a  permanent  yellow,  although  no  more  mer- 
curic nitrate  be  added.  Under  those  circumstances  the  analysis 
must  be  repeated,  taking  the  first  titration  as  a  guide  to  the 
quantities  that  are  necessary.  Pfluger's  correction  for  concen- 
tration of  urea  is  different  from  Liebig's,  and  is  as  follows: 

V^  =  volume  of  urea  solution  -f-  volume  of  sodium  carbonate 
solution  -(-  volume  of  any  other  fluid  free  from  urea  that  may 
be  added. 

V2  =  volume  of  mercuric  nitrate  solution  used. 

C  =  correction  =  —  (V^  —  V2)  x  0.08. 
4 


50  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

This  formula  holds  good  for  cases  in  which  the  total  mixture 
is  less  than  three  times  the  volume  of  mercuric  nitrate  solution 
used  ;  with  more  concentrated  solutions  the  formula  gives  results 
too  high. 

Pfliiger  and  Bleibtreu  ^  have,  recently,  in  a  series  of  papers, 
introduced  fresh  methods  of  urea  analysis  of  so  complex  a 
nature  that  they  are  quite  unsuitable  for  ordinary  clinical  work. 

Liebig's  method  is  by  far  the  most  accurate  for  the  quantita- 
tive determination  of  urea,  but  it  is  too  long  and  complicated 
for  clinical  purposes. 

(b)  The   Hypobromite  or  Hypochlorite   Method. — 

The  principle  upon  which  this  method  is  based  is  that  urea, 
when  brought  in  contact  with  sodium  hypobromite  or 
sodium  hypochlorite,  is  decomposed  into  nitrogen,  carbon 
dioxide,  and  water.     Thus  : 

CH.Np  +  jNaOBr  =.  aNaBr  +  CO^  +  N,  +  2U,0, 

the  volume  of  nitrogen  disengaged  being  the  measure  of 
the  urea.  The  carbon  dioxide  set  free  immediately  com- 
bines with  the  excess  of  sodic  hydrate  in  the  hypobromite 
mixture  used,  and  forms  sodium  carbonate,  which  remains 
in  solution. 

All  quantitative  determinations  by  this  method  are  de- 
pendent upon  the  fact  that  one  cubic  centimeter  of  nitrogen 
gas  at  the  standard  temperature  and  pressure  is  equivalent 
to  0.0027  gram  of  urea  ;  or,  on  the  other  hand,  that  one 
gram  of  urea  at  0°  C.  furnishes  370  c.c.  of  nitrogen. 

Various  forms  of  apparatus  for  the  application  of  this 
process  have  been  devised,  among  which  are  those  of 
Hiifner,  Gerrard,  Dupre,  W.  H.  Greene,  Charles  A.  Dore- 
mus,  E.  R.  Squibb,  and  others.  In  the  use  of  these  vari- 
ous forms  only  approximate  results  are  obtained,  but  the 
one  devised  by  E.  R.  Squibb  is  by  far  the  most  satisfactory 
for  clinical  purposes. 

Sqiiibli's  Apparatus'^  (^ig-  4)- — This  apparatus  consists 
of  two  two-ounce  bottles,  a  and  h,  each  being  supplied  with 
a  double-bored  rubber  stopper  and  connected  by  means  of 
a  rubber  tube,  <r;  a  2  c.c.  pipette  that  is  closed  at  its 
upper  end  by  a  nipple  ;  a  30  c.c.  graduate,  g,  into  which  a 

^  "Pfliiger's  Archiv,"  XLiv,  S.  i. 

2  This  apparatus  can  be  purchased  of  E.  R.  Squibb  &  Sons,  Brooklyn, 
N.  Y.,  or  of  Messrs.  Eimer  &  Amend,  205-211  Third  Avenue,  New  York 
city,  at  a  moderate  cost. 


QUANTITATIVE   DETERMINATION   OF   UREA. 


51 


rubber  tube,  d,  extends  from  bottle  b ;   and  a  small   glass 
plug,  c. 

Reagents. — Among  the  reagents  that  may  be  used  for  decom- 
posing the  urea  in  urine  by  this  apparatus,  the  following  are  the 
most  convenient  and  the  best : 

I.  The  Solution  of  Chlorinated  Soda  of  the  United  States 
Pharmacopeia  of  1840  to  1870  inclusive,  but  the  solution  of  the 
U.  S.  P.  of  1880  must  be  avoided,  as  it  will  not  answer  the  pur- 
pose at  all.  If  this  solution  of  1870  is  not  accessible  when  this 
apparatus  is  to  be  used,  it  may  be  extemporaneously  made  by 
the  following  formula  and  process  from  the   chlorinated    lime 


Fig. '4. — Squibb's  urea  apparatus,  for  the  approximate  estimation  of  urea  in  urine. 


supplied  with  the  apparatus,  or  from  any  other  source.  Fifteen 
or  twenty  cubic  centimeters  of  this  solution  are  sufficient  for  each 
assay. 

2.  Extemporaneous  Solution  of  Chlorinated  Soda:  Take  of 
chlorinated  lime  (chloride  of  lime  or  bleaching  powder)  20 
grams,  or  318  grains  ;  and  sodium  carbonate  (common  washing 
soda,  or  "sal  soda"),  40  grams,  or  636  grains.  Shake  the 
chlorinated  lime  in  a  bottle  with  45  c.c.  or  i^/^  fluidounces 
of  water  until  thoroughly  disintegrated.  Allow  the  mixture 
to  settle  for  a  minute  or  two,  and  pour  the  thin  portion 
upon  a  paper  filter  in  a  funnel,  filtering  into  a  bottle  of  about 
100    c.c.    capacity.      Shake   the    thick    residue   remaining    in 


52  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

the  bottle  with  30  c.c.  or  i  fluidounce  more  water,  and  when 
the  first  portion  on  the  filter  has  drained  through,  pour  the 
whole  of  the  second  portion  on  the  filter  and  allow  this  to  drain 
through.  Then  dissolve  the  sodium  carbonate  in  30  c.c,  or  i 
fluidounce,  of  hot  water,  and  add  this  solution  to  the  filtrate  in 
the  first  bottle.  Shake  the  solutions  well,  and  if  the  mixture 
gelatinizes,  warm  the  bottle  and  shake  until  it  liquefies,  and 
then  pour  it  upon  a  new  filter-paper,  filtering  off  the  clear  solu- 
tion into  a  bottle  marked  at  100  c.c.  When  the  filtrate  has 
drained  through,  pour  water  into  the  filter  until  the  filtrate 
reaches  the  100  c.c.  mark  on  the  bottle.  This  solution  is  about 
equivalent  to  that  of  the  U.  S.  P.  of  1870  for  this  assay,  and 
when  recently  made,  10  c.c.  of  it  are  sufficient  for  each  assay,  but 
when  old  or  made  from  old  chlorinated  lime,  15  c.c.  are  a  safer 
quantity. 

3.  Solution  of  Chlorinated  Lime  :  Take  of  chlorinated  lime 
("  chloride  of  lime  ")  40  grams,  or  617  grains  ;  water,  a  suffi- 
cient quantity.  Shake  the  chlorinated  lime  well  with  120  c.c, 
or  4  fluidounces,  of  water,  and  after  the  mixture  has  settled  for 
a  minute  or  two  pour  off  the  thinner  portion  on  to  a  filter-paper, 
and  filter  into  a  bottle  marked  at  200  c.c,  or  6fi  fluidounces. 
Add  80  c.c.  more  water  to  the  thick  residue  of  the  chlorinated 
lime,  again  shake  well,  and  pour  the  whole  upon  the  filter  after 
the  first  portion  has  nearly  all  drained  through.  When  the 
second  portion  has  drained  through,  pour  water  on  the  residue 
in  the  filter  until  the  filtrate  reaches  the  200  c.c.  mark  on  the 
bottle.  Then  cork  the  bottle  and  shake  it,  label  it,  and  date 
the  label. 

For  the  decomposition  of  urea  this  solution  is  the  best  of  all 
reagents  yet  tried.  It  is  very  efficient  when  a  month  old,  but 
how  much  longer  it  will  retain  its  efficiency  is  not  known.  Its 
reaction  with  the  urea  is  very  prompt,  and  is  divided  into  two 
stages  of  very  active  reaction,  which  are  usually  from  one  to 
three  minutes  apart.  Then  the  end  reaction  is  fairly  sharp. 
The  whole  time  of  shaking  is  usually  not  over  six  minutes,  and 
a  warm  bath  is  not  needed.  Even  when  made  from  18  per 
cent,  chlorinated  lime,  10  c.c  of  this  solution  are  quite  sufficient 
for  an  assay,  and,  therefore,  the  foregoing  formula  yields  enough 
for  20  assays  ;  the  bottle  of  chlorinated  lime  supplied  with  the 
apparatus  contains  about  enough  to  make  solution  for  40  assays 
before  it  will  need  replenishing. 

4.  Solution  of  Sodium  Hypobromite:  This,  as  applied  by 
the  improved  process  of  Dr.  Charles  Rice,  is  kept  in  two  sepa- 
rate solutions,  which  are  mixed  shortly  before  using  them. 

{a)  The  solution  of  caustic  soda  is  made  by  dissolving  100 
grams  of  caustic  soda  in  250  c.c.  of  water,  the  resulting  solution 
measuring  about  284  c.c. 


UREA.  53 

(^b)  The  solution  of  bromine  is  made  as  follows :  Bromine 
is  commonly  sold  in  one-ounce  glass-stoppered  vials,  which, 
on  an  average,  contain  less  than  an  ounce ;  the  quantity  must 
be  ascertained  by  weighing  the  vial  and  contents  after  the 
stopper  is  loosened,  pouring  the  contents  into  a  bottle  of  about 
300  c.c,  or  10  fluidounces,  capacity,  and  then  weighing  the 
empty  vial,  and  subtracting  its  weight.  Then  add  to  the 
bromine  in  the  bottle  an  equal  weight  of  either  sodium  bromide 
or  potassium  bromide,  and  as  many  cubic  centimeters  of  water 
as  eight  times  the  nmiiber  of  grams  of  the  bromine,  and  shake 
until  the  bromine  is  dissolved,  when  the  solution  is  ready  for 
use. 

For  the  assay  this  and  the  soda  solutions  are  taken  in  equal 
measures,  and  are  mixed,  near  the  time  of  using,  in  any  desired 
quantity.  If  but  one  or  two  assays  are  to  be  made,  they  may 
be  measured  directly  into  bottle  a,  and  be  mixed  there,  using 
the  measuring  jar  for  the  purpose.  While  2.5  c.c.  of  each  solu- 
tion with  5  c.c.  of  water,  or  3.5  c.c.  of  each  solution  with  3  c.c. 
of  water,  are  sufficient  for  an  assay,  it  is  better  to  take  5  c.c.  of 
each  solution  for  safety,  and  not  dilute  with  water.  The  reaction 
is  very  prompt,  and  the  end  reaction  is  fairly  definite  and  sharp, 
and  there  is  no  perceptible  double  reaction  with  an  interval 
between  them,  as  in  the  chlorinated  lime  solution,  unless  there 
is  a  larger  dilution.  So  long  as  these  solutions  are  not  mixed 
they  will  keep  indefinitely,  and,  therefore,  when  the  trouble  of 
making  them  is  over,  they  are  very  convenient  for  use,  the  results 
being  more  uniform,  but  a  trifle  lower,  than  those  from  the  solu- 
tion of  chlorinated  lime. 

Process. — i.  Provide  a  vessel  containing  enough  water  to  im- 
merse bottle  a,  the  water  being  at  room-temperature, — or  about 
18°  C-  (64.4°  F. ), — to  be  used  as  a  cold  bath. 

2.  Put  one  end  of  the  short  rubber  tube  d  on  the  bent  glass 
tube  of  the  stopper  of  the  bottle  b,  and  slip  it  on  the  glass  tube 
just 'SO  far  that  when  the  bottle  b  is  laid  on  its  side  on  its  sup- 
port, the  free  end  of  the  rubber  tube  will  just  clear  the  bottom 
of  the  measuring  jar,  as  shown  in  the  cut. 

3.  Fill  the  bottle  b  with  water  at  room-temperature,  and  put 
the  stopper  firmly  in  place,  allowing  the  displaced  water  to 
escape  through  the  tubes.  Then,  taking  the  bottle  in  the  right 
hand  with  the  forefinger  over  the  end  of  the  straight  glass  tube 
of  the  stopper,  incline  the  bottle  toward  the  bent  glass  tube, 
and  relax  the  pressure  of  the  forefinger  on  the  end  of  the 
straight  tube  so  that  water  enough  may  escape  to  completely  fill 
the  rubber  tube  d.  Then  with  the  left  hand  put  the  little  glass 
stopper  e  in  the  free  end  of  ^  and  lay  bottle  /^  thus  filled,  on  its 
support ;  this  requirement  may  be  fulfilled  by  the  lid  of  the 
box. 


54  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

4.  Next,  put  one  end  of  the  long  piece  of  rubber  tubing  {c) 
on  the  bent  glass  tube  of  the  stopper  of  the  bottle  a. 

5.  Measure  out  in  the  graduate  the  quantity  of  the  reagent  to 
be  used,  and  having  poured  it  into  bottle  a,  rinse  out  the  grad- 
uate-glass. 

6.  Dip  the  stopper  of  bottle  a  into  water,  and  put  it  loosely 
in  its  place. 

7.  Dip  the  mouth  of  the  rubber  bulb  of  the  pipette  in  water 
for  lubrication,  and  put  the  bulb  on  the  pipette  nearly  as  far  as  it 
will  go.  Compress  the  large  part  of  the  bulb  upon  the  pipette, 
and  having  dipped  the  point  in  the  urine,  relax  the  compression 
entirely.  The  expansion  of  the  bulb  will  cause  the  urine  to 
rise  and  fill — or  nearly  fill — the  body  of  the  pipette.  Then,  tak- 
ing the  body  of  the  pipette  between  the  left  thumb  and  fingers 
while  the  point  is  still  immersed  in  the  urine,  with  the  right 
thumb  and  forefinger  applied  to  the  rubber  ring  at  the  mouth  of 
the  bulb,  screw  the  bulb  upward  on  the  pipette  so  that  the  urine 
may  slowly  rise  to  the  mark  until  the  lower  limb  of  the  menis- 
cus lies  just  above  the  mark.  Now,  when  the  point  of  the  pipette 
is  raised  out  of  the  urine,  the  meniscus  will  fall  a  little,  and  lie 
exactly  on  the  mark.  Then  screw  the  bulb  a  little  higher,  so 
that  a  very  little  air  may  enter  the  point  of  the  pipette,  to  prevent 
loss  of  the  measured  urine. 

8.  Pass  the  lower  end  of  the  charged  pipette  through  the 
vacant  hole  in  the  stopper  of  bottle  a,  and  then  screw  the  stop- 
per into  its  place  by  holding  the  stopper  firmly,  and  turning  the 
bottle  upon  it. 

9.  Then  put  the  free  end  of  the  long  rubber  tube  c  on  the 
end  of  the  straight  glass  tube  of  the  stopper  of  bottle  b,  thus 
connecting  a  and  b. 

10.  Next,  take  out  the  little  glass  stopper  e  from  the  free 
end  of  the  short  rubber  tube  d,  and  allow  the  few  drops  of  water 
that  will  flow  to  escape,  seeing  that  the  flow  ceases  completely. 

11.  Then  put  the  empty  measuring  jar  in  its  place  under  the 
tube  d,  to  receive  the  displaced  water  of  the  process,  when  the 
preparation  for  the  process  will  be  complete. 

12.  Take  the  bottle  a  by  the  neck,  between  the  right  thumb 
and  forefinger,  and  take  the  upper  part  of  the  pipette  with  the 
left  thumb  and  fingers,  in  readiness  to  compress  the  rubber  bulb, 
shaking  the  lower  part  of  the  bottle  from  side  to  side,  and  not 
up  and  down.  During  this  gentle  shaking  compress  the  bulb, 
so  as  to  force  all  the  urine  out  of  the  pipette  into  the  bottle 
with  the  reagent.  Active  effervescence  will  soon  commence, 
and  while  it  is  active  relax  the  compression  of  the  bulb  gradu- 
ally and  completely.  If  this  be  properly  done,  no  liquid — or 
but  a  drop  or  two — will  get  into  the  rubber  tube  to  be  carried 
over  into  bottle  b.     Continue  the  shaking  as  long  as  bubbles  of 


UREA.  55 

gas  pass  over  into  bottle  b.  If  chlorinated  soda  solution  be 
used  as  the  reagent  and  without  a  warm  bath,  the  shaking  will 
require  from  twenty  to  thirty  minutes;  but  with  the  warm  bath, 
not  more  than  from  six  to  eight  minutes. 

13.  Bottle  a  is  then  immersed  in  the  cold  bath,  at  about  18° 
C.  (64.4°  F.),  for  about  four  minutes.  During  this  immersion 
the  contraction  in  bottle  a  will  draw  water  from  bottle  b  into  a 
and  from  the  measuring  jar  back  into  bottle  b,  and  when  there 
is  no  longer  any  change  in  tlie  measuring  jar,  the  contraction  is 
finished. 

14.  The  bottles  are  removed  and  set  aside  to  be  prepared 
for  a  new  assay ;  and  the  contents  of  the  measuring  jar  are 
carefully  read  off  to  half  a  cubic  centimeter,  and  the  quantity 
thus  obtained  is  noted  and  referred  to  the  first  column  of  the 
urea  table.  There  the  proportion  of  urea  present  is  found 
calculated  in  percentage,  and  in  grams  and  grains  for  various 
measures  of  urine.  For  example,  if  the  graduate-glass  contains 
16  c.c.  of  displaced  water,  from  the  urea  table  it  will  be  found 
that  the  urine  contains  2.02  percent,  of  urea,  or  0.621 2  grams  in 
30  c.c.  of  urine,    (^d)  If  the  twenty-four-hour  quantity  of  urine  be 

1  1  1         •  r  1  ISOO  V  2.02 

1500  c.c,  then  calculating  from  the  percentage  — — — =  IP -IP 

grams,  which  represents  the  app7'oximate  number  of  grams  of 
urea  in    twenty-four  hours,      {b')  Or,  calculating  from  the  third 

1          -1        11     o.62i2Vi';oo  r  ,  .  , 

column  in  the  table, —  S^-oo  grams,  which  represents 

the  accurate  number  of  grams  of  urea  in  twenty-four  hours. 


TABLE  OF   APPROXIMATE   PROPORTIONS  OF   UREA   IN 
URINE,   FOR  CLINICAL  USE. 

One  cubic  centimeter  of  nitrogen  gas  at  0°  C.  (32°  F.)  equals  0.0027  grana 
of  urea. 

Assumed  room- temperature  for  measurements,  18°  C.  (64.4°  F.). 

Rate  of  expansion,  0.003663  times  the  volume  for  each  I°C.  Correction 
applied  for  18°  C.  (64.4°  F.)  is  0.003663  X  18  =0.0659  subtracted  for  each 
I. c.c.  as  read  off  from  the  measuring  jar,  and  the  percentage  is  calculated  from 
the  corrected  reading. 

Thirty  cubic  centimeters  are  assumed  as  equal  to  one  fluidounce,  but  in  con- 
verting any  considerable  quantities  from  one  measure  to  the  other  29.52  c.c. 
should  be  taken  as  one  fluidounce. 

In  converting  measures  to  weights,  and  in  using  measures  and  weights  to- 
gether, an  assumed  specific  gravity  for  abnormal  urine  is  taken — namely,  1025 
at  25°  C.  (77°  F. )  ;  and  30  c.c.  of  urine  of  such  specific  gravity  weigh  30.75 
grams,  and  one  fluidounce  weighs  467.4  grains. 

Four  hundred  and  seventy-three  cubic  centimeters  are  as.suined  as  equal  to 
one  pint,  or  sixteen  fluidounces,  and  when  these  measures  are  used  for  urine, 
they  are  assumed  as  weighing  484.83  grams  (1025  x  473)  and  7478.4  grains 
(467.4  X  16)  respectively. 

The  seventh  and  eighth  columns  must  not  be  taken  as  having  any  definite 
relation  to,  or  bearing  upon,  the  assay,  excepting  when  the  total  twenty-four- 


56 


ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 


hour  excretion  amounts  to  just  Il8l  c.c,  or  40  fluidounces,  or  very  near  to  this 
measure,  as  the  calculations  are  based  upon  this  arbitrary  quantity. 


E< 

0 
U 

Urea  Con- 

Urea 

CON- 

Urea  Con- 

Hi2 

a 

tained  IN  30 

TAINED 

IN  473 

tained  IN  II8I 

to   Q              .-^ 

fc  <J  , 

u 

c.c,  OR  I  Fluid- 

c.c,  OR 

I  Pint, 

C.C, 

OR  40 

^  f?  u    .  W 

ZO  J  «  J 

0  z  'J 

(J 

<  < 

ounce,  OF 

OF  URINR. 

Fluidounces, 

Offish" 

o2u 

U 

Uri 

NE. 

OF  Urine.      | 

SS^; 

OS 

a: 
0 
U 

(d 

m  CS  Q  0 
H  ^  .  <  a: 

5;  (fl  ^ 
5  < 

05^ 

In 

In 

In 

In 

In 

In 

0. 

Grams. 

Grains. 

Grams. 

Grains. 

Grams. 

Grains. 

jwS 

4  c 

c. 

0.50 

0.1538 

2.34 

2.425 

37-44 

6.055 

93.60 

5    ' 

0.63 

0-1937 

2.94 

3-054 

47.04 

7.625 

117.60 

6    ' 

0.76 

0-2337 

3-55 

3-685 

56.80 

9.200 

142.00 

7 

0.88 

0.2706 

4-11 

4.267 

65.76 

10.653 

164.40 

8    ' 

1. 01 

0  3106 

4.72 

4.897 

75-52 

12.227 

188.80 

9    ' 

1-13 

0.3475 

5-28 

5-479 

84.48 

13.680 

211.20 

10    ' 

1.26 

0-3875 

5-89 

6. no 

94-24 

15  255 

235.60 

II     ' 

1-39 

0.4274 

6.50 

6-739 

104.00 

16.825 

260.00 

12    ' 

I-5I 

0.4643 

7.06 

7-321 

112.96 

18.278 

282.40 

13     ' 

1.64 

0-5043 

7.67 

7951 

122.72 

19.853 

306.80 

Lowest. 

14    ' 

1-77 

0.5443 

8.27 

8.582 

132-32 

21.427 

33080 

15    ' 

1.89 

0.5812 

8.83 

9.164 

141.28 

22.880 

353-20 

16    ' 

2.02 

0.6212 

9-44 

9-794 

151.04 

24.455 

377-60 

17    ' 

2.14 

0.6581 

10.00 

10.376 

160.00 

25.907 

400.00 

18    ' 

2.27 

0.6980 

10.61 

11.005 

169.76 

27.478 

424.40 

19    ' 

2.40 

0.7380 

11.22 

11.636 

179-52 

29-053 

448.80 

20    ' 

2.52 

0.7749 

11.78 

12.218 

188.48 

30-505 

471.20 

Normal. 

21     ' 

2.65 

0.8149 

12.39 

12.849 

198.24 

32.080 

495-60 

.22    ' 

2.77 

0.S518 

12-95 

13-430 

207.20 

33-533 

518.00 

23    ' 

2.90 

0.8918 

13-55 

14.061 

216.80 

35-107 

542-00 

24 

3-03 

0-9317 

14.16 

14.690 

226.56 

36.678 

566.40 

25    ' 

3-15 

0.9686 

14.72 

15.272 

235-52 

38-131 

58S.80 

.   .   . 

26 

3-28 

1.0086 

15-33 

15-903 

245.28 

39.706 

613.20 

27 

340 

1-0455 

15-89 

16.484 

254.24 

41.158 

635.60 

Highest. 

Dorenius  Urcovictcr. — The  apparatus  as  represented  in 
figure  5  was  devised  by  Dr.  Charles  A.  Doremus,  of  New- 
York.  It  is  much  used  for  rapid  chnical  purposes,  and 
consists  of  a  bulb  with  an  upright  graduated  tube,  and  a 
small  nipple-pipette  to  hold  one  cubic  centimeter  of  urine. 
The  tube  is  so  graduated  that  each  of  the  small  divisions 
represents  o.OOl  gram  of  urea.  The  bulb  is  filled  with 
the  sodium  hypobromite  solution,  and  the  apparatus  in- 
clined sufficiently  to  fill  the  upright  graduated  tube,  and 
then  water  is  added  to  fill  the  remainder  of  the  tube  and 
lower  part  of  the  bulb.  The  pipette  is  filled  with  urine  to 
the  one  cubic  centimeter  mark,  and  the  point  carefully  in- 
troduced into  the  bend  as  far  as  it  will  go,  holding  the 
graduated  tube  perpendicularly.  The  nipple  is  then  slowly 
compressed  to  expel  all  of  the  urine,  care  being  taken  not 
to  force  air  into  the  tube  after  the  urine  has  been  expelled. 
The  pipette  is  then  withdrawn,  and  after  the  evolution  of  gas 
is  complete  the  number  of  cubic   centimeters   of  nitrogen 


UREA. 


57 


gas  is  read  off,  and  the  result  multiplied  by  lOO  in  order  to 
obtain  the  percentage  of  urea.  Two  forms  of  this  appa- 
ratus are  obtainable — one  graduated  to  read  fractions  of  a 
gram  per  cubic  centimeter  of  urine,  and  the  other  gradu- 
ated to  read  the  number  of  grains  of  urea  per  fluidounce 
of  urine. 

The  Dorcnius  urcomctcr  as  modified  by  Professor  J.  D. 
Hinds  (Fig.  6)  has  many  advantages  over  the  original  form 
of  apparatus.  This  instrument  consists  of  a  bulb  with  an 
upright  graduated  tube  («),  the  same  as  the  original  ;  near 
the  lower  portion  of  this  tube  is  a  horizontal  glass  connec- 


Fig.  5. — Doremus  ureometer. 


Fig.  6. — Hinds'  modification  of  the  Dore- 
mus ureometer. 


tion,  which  is  provided  with  a  ground  glass  stop-cock  {S), 
and  wdiich  supports  another  upright  graduated  tube  (r) 
with  a  capacity  of  two  cubic  centimeters.  The  bulb  and 
upright  tube  {a)  are  filled  with  the  sodium  hypobromite  solu- 
tion in  precisely  the  same  manner  as  previously  described. 
The  upright  tube  {c)  is  then  filled  to  the  zero  mark  with 
the  urine  to  be  tested.  The  stop-cock  (^)  is  then  turned, 
and  exactly  one  cubic  centimeter  of  the  urine  allowed  to 
enter  tube  a  with  the  reagent.  As  soon  as  the  evolution 
of  nitrogen  gas  is   complete,  the  number  of  cubic   centi- 


58  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

meters  of  the  gas  is  read  off,  and  the  result  multiplied  by 
lOO  in  order  to  obtain  the  percentage  of  urea. 

This  form  of  apparatus  ^  gives  more  exact  results  than  the 
original  form,  since  the  one  cubic  centimeter  of  urine  re- 
quired for  the  test  is  delivered  with  greater  accuracy,  and 
no  nitrogen  gas  is  lost  by  its  escape  from  the  bulb. 

(c)  Fowler's  Hypochlorite  Method  (Differential 
Density).'^ — This  method  is  based  upon  the  fact  that  there 
is  a  difference  in  the  specific  gravity  of  urine  before  and 
after  the  decomposition  of  its  urea  by  the  hypochlorites  ; 
and  that  such  difference  bears  a  definite  relation  to  the 
quantity  of  urea  present.  Dr.  Fowler  found  that  every 
degree  of  density  lost  corresponds  to  0.77  of  one  per  cent., 
or  about  3 1^  grains  per  fluidounce.  The  hypochlorite 
solution  employed  is  Squibb's  solution  of  chlorinated  soda, 
or  Labarraque's  solution,  of  which  seven  parts  will  decom- 
pose the  urea  in  one  part  of  urine,  unless  the  amount  is 
very  large,  in  which  event  the  urine  should  be  diluted  by  an 
equal  bulk  of  water,  and  the  result  multiplied  by  2.  The 
presence  of  albumin  and  sugar  does  not  interfere  with  this 
test. 

Process. — i.  Add  to  i  volume  of  the  urine  7  volumes 
of  the  hypochlorite  solution  ;  effervescence  due  to  the  liber- 
ation of  nitrogen  will  immediately  take  place.  Shake  the 
jar  containing  the  mixture  occasionally,  and  stand  it  aside 
for  two  hours,  when  the  urea  will  have  been  decomposed. 
Now  take  the  specific  gravity  of  the  quiescent  fluid. 

2.  Ascertain  the  specific  gravity  of  the  mixed  urine  and 
hypochlorite  solution  before  decomposition.  To  do  this, 
multiply  the  specific  gravity  of  the  pure  hypochlorite  solu- 
tion by  7,  add  this  to  the  specific  gravity  of  the  pure  urine, 
and  divide  by  8.  The  result  is  the  specific  gravity  of  the 
mixed  fluid.  From  this  subtract  the  specific  gravity  of  the 
quiescent  mixture  after  decomposition  of  the  urea,  multiply 
the  difference  by  0.77,  and  the  result  is  the  percentage  of 
urea  ;  or  by  3  ^,  which  gives  the  quantity  of  urea  in  grains 
per  fluidounce. 

1  This  instrument,  as  well  as  the  original  Doremus  ureometer,  can  be  ob- 
tained at  a  moderate  cost  from  Messrs.  Eimer  &  Amend,  205  to  211  Third 
Ave.,  New  York  city. 

2  Fowler,  "  Prize  Essay  to  the  Alumni  Association  of  the  College  of  Physi- 
cians and  Surgeons,"  New  York.  Published  in  the  "New  York  Medical 
Journal,"  July,  1887. 


URIC  ACID.  59 

As  changes  of  temperature  affect  the  specific  gravity 
and  volume  of  hquids,  the  hypochlorite  solution  and  urine 
should  be  mixed,  and  the  jar  set  aside  along  with  a  bottle 
of  the  urine  and  the  hypochlorite  solution  in  the  same 
place,  subject  to  the  same  temperature.  When  decomposi- 
tion is  complete,  the  specific  gravities  can  be  taken,  and  the 
calculation  made. 

Example. — Suppose  the  specific  gravity  of  the  urine  is 
loio,  and  that  of  the  hypochlorite  solution  is  1045,  that 
of  the  mixed  fluid  will  be 

1045  X  7  +  loio 

3     =  1040. 

Now  suppose  the  specific  gravity  of  the  decomposed  fluid 
is  1038,  then  (1040 —  1038)  X  0.77  =  1.54,  the  percent- 
age of  urea. 


URIC  ACID. 

CjHiNiOs. 

Uric  acid  (H2U,  expressed  also  U)  is,  in  mammals,  next 
to  urea,  the  medium  by  which  the  largest  quantity  of  nitro- 
gen is  excreted  from  the  body.  It  is,  however,  in  birds 
and  reptiles  the  principal  nitrogenous  constituent  of  the 
urine. 

Until  recently,  the  theory  of  the  formation  of  uric  acid 
was  that  it  was  a  product  of  the  metabolism  of  the  nitro- 
genous material  ingested,  and  that  it  represented  an  inter- 
mediate product  between  the  nitrogenous  substances  and 
the  final  product,  urea.  The  researches  of  Horbaczewski,! 
Hopkins  and  Hope,^  Jerome,^  and  others  tend  to  show 
that  uric  acid  has  an  entirely  different  origin.  It  is  now 
believed  that  uric  acid  is  at  least  partly  derived  from  the 
nucleins  that  form  a  constituent  of  all  cell-nuclei,  and  which 
are  taken  into  the  body  as  food.  The  nucleins  are  capable 
of  being  split  up  into  an  albumin  and  nucleic  acid,  and  it  is 
thought  that  the  uric  acid  is  formed  in  the  body  from  the 
nucleic  acid  through  the  oxidation  of  the  xanthin  or  alloxur 
groups  contained  in  a  molecule  of  nucleic  acid.  It  has 
been  demonstrated  that  the  ingestion  of  food  that  is  rich  in 
nucleins  results  in  the  formation  and  elimination  of  a  much 

1  "  Monatsh.  f.  Chem.,"  S.  624,  1889.       2  "  Journ.  of  Physiol.,"  XXIII,  p.  271. 
3  "Journ.  of  Physiol.,"  xxil,  p.  146. 


60  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

larger  quantity  of  uric  acid  than  the  ingestion  of  an  equal 
amount  of  food  that  is  poor  in  nucleins.  The  chief  evi- 
dence, however,  in  favor  of  the  view  that  nucleins  play  a 
role  as  precursors  of  uric  acid  is  based  upon  the  results  of 
thymus  feeding.  The  experiments  of  Hopkins  and  Hope, 
however,  show  that  extracts  of  the  thymus  gland  may  be 
prepared  which  contain  only  traces  of  nucleins  and  nucleic 
acid,  but  which,  when  ingested,  produce  the  characteristic- 
ally large  excretion  of  uric  acid.  It,  therefore,  appears 
that  some  more  soluble  constituent  of  the  diet  acts  either 
as  a  direct  precursor,  or  as  a  factor  in  the  formation  of 
uric  acid. 

Our  knowledge  of  this  subject  is  yet  too  meager  to  war- 
rant the  conclusion  that  this  new  theory  fully  explains  the 
formation  of  uric  acid,  but  there  can  be  no  doubt  that  the 
nucleins  (nucleic  acid)  play  an  important  part  in  its  forma- 
tion. 

When  uric  acid  is  referred  to  as  a  constituent  of  normal 
urine,  it  is  never  to  its  free  state  that  allusion  is  made,  but 
to  its  combinations  chiefly  with  potassium,  sodium,  and 
ammonium,  and  also  with  calcium  and  magnesium  ;  such 
combinations  being  usually  known  as  mixed  urates. 

Under  ordinary  conditions  uric  acid  exists  in  the  urine  in 
the  form  of  urates.  Since  uric  acid  is  dibasic, — that  is,  has 
two  replaceable  atoms  of  hydrogen, — two  forms  of  salts 
exist — i.  e.,  acid  urates  of  potassium,  sodium,  and  ammo- 
nium, in  which  only  one  atom  of  the  hydrogen  is  replaced 
by  the  positive  elements  or  radicles  ;  and  normal  (neutral) 
salts  of  the  same  substances,  in  which  both  atoms  of  hydro- 
gen are  replaced.  According  to  Neubauer  and  Vogel, 
there  are  two  forms  of  acid  urates — monacid  urates  (bi- 
urate),  and  triacid  urates  (quadriurate  or  tetraurate).  The 
normal  salts  are  readily  soluble  in  water  at  70°  F.,  but  the 
acid  urates  are  only  feebly  soluble,  while  uric  acid  itself  is 
almost  insoluble  in  water.  Hence,  the  precipitation  of  the 
acid  urates  or  uric  acid  often  occurs  w^hen  the  urine  cools, 
or  is  allowed  to  stand  in  a  cold  place.  A  urine  containing 
a  deposit  of  acid  urates  (amorphous  urates)  is  usually  more 
or  less  concentrated,  and  always  contains  a  relative  excess 
of  the  acid  urates.  If  a  strong  acid  be  added  to  a  urine 
that  contains  a  relative  excess  of  urates,  they  are  precipi- 
tated on  account  of  the  feeble  solubility  of  the  acid  urates 
and  the  almost  insoluble  uric  acid.     Also,  if  the  urine  con- 


URIC  ACID.  61 

tains  an  excess  of  normal  urates,  they  are  partially  decom- 
posed by  the  acid,  which  chemically  unites  with  the  excess 
of  the  base  to  form  acid  urates,  hence  their  precipitation. 
Thus,  in  the  nitric-acid  test  for  albumin  (performed  accord- 
ing to  instructions  given  on  p.  122)  a  white  zone  of  acid 
urates  is  frequently  seen  above  the  zone  of  albumin  (Fig. 
I  5),  or  above  where  the  zone  of  albumin  would  be  if  pres- 
ent. It  should  be  borne  in  mind  that  a  zone  of  urates  may 
be  present  when  albumin  is  absent. 

Pure  uric  acid  is  soluble  in  16,000  parts  of  cold  water 
and  in  1600  parts  of  boiling  water;  impure  uric  acid  is 
more  readily  soluble  in  water  than  the  pure.  Its  cold  solu- 
tions do  not  show  an  acid  reaction  with  litmus  paper.  Uric 
acid  is  insoluble  in  alcohol  and  ether,  but  dissolves  in  warm 
glycerin,  from  which,  on  cooling,  it  separates  in  crystalline 
form.  It  is  insoluble  in  strong  mineral  acids,  but  is  soluble 
in  alkaline  hydrates  as  well  as  in  alkaline  carbonates,  phos- 
phates, lactates,  and  acetates.  It  is  more  soluble  in  solu- 
tions of  urea  than  in  water  (Riidel). 

On  boiling,  uric  acid  reduces  alkaline  solutions  of  copper  ; 
before  reduction  occurs,  however,  a  white  precipitate,  con- 
sisting of  cuprous  urate,  is  formed. 

When  uric  acid  is  artificially  decomposed,  an  interesting 
series  of  products  results,  the  most  important  of  which  is 
urea.  Whether  similar  changes  take  place  in  the  body  is 
still  a  matter  of  doubt. 

The  following  is  a  list  of  the  principal  changes  which 
may  be  brought  about  by  various  reagents  : 

1.  When  uric  acid  is  reduced  with  weak  sodium  amalgam, 
two  substances — xanthin  (C^H^N^O^)  and  hypoxanthin  or  sar- 
kin  (CjH^N^O) — may  be  obtained.  Their  formulas  differ  from 
that  of  uric  acid  in  containing  one  or  two  atoms  less  oxygen  re- 
spectively than  that  substance. 

2.  When  uric  acid  is  heated  in  a  closed  tube  with  hydro- 
chloric acid,  it  is  decomposed  into  glycocoll,  carbolic  acid,  and 
ammonia: 

C,U,^fi,  +  5H,0  =  C3H.NO,  +  3CO,  -f-  3NH3. 

3.  By  the  action  of  cold,  concentrated  nitric  acid,  uric  acid 
takes  up  water  and  oxygen,  forming  alloxan  and  urea  : 

2CjH,N,03  4-  2H,,0  -f  O,  =  2C,H„N,0^  -}-  aCON^H^. 
Uric  acid.  Alloxan.  Urea. 


62  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

Alloxan,  when  boiled  with  a  strong  alkali,  takes  up  water  and 
is  decomposed,  forming  mesoxalic  acid  and  urea: 

2C,H,N,0,  +  4H,0  =  aCgH.O,  ^   2CON,H,. 

Alloxan.  Mesoxalic  Urea, 

acid. 

On  oxidation,  mesoxalic  acid  forms  oxalic  and  carbonic  acids  : 

2C3H2O5  +  O2  =  2C.,H.,0^  ^  2CO,. 

Thus,  it  is  seen  that  in  three  steps  the  ultimate  products  of 
uric  acid  are  urea,  oxalic  acid,  and  carbonic  acid. 

4.  There  is  another  way  in  which  the  same  three  ultimate 
products  are  obtained,  but  the  intermediate  step  in  the  process 
is  not  the  formation  of  alloxan,  but  of  another  somewhat  similar 
substance  called  allantoin.  This  process  is  interesting,  as  allan- 
toin  is  in  fetal  life  one  of  the  products  of  nitrogenous  metabol- 
ism, and  it  is  thus  possible  that  some  sort  of  change,  such  as 
can  be  produced  artificially,  occurs  in  embryonic  life. 

Uric  acid  when  oxidized  with  potassium  permanganate  (care 
being  taken  that  the  temperature  does  not  rise)  takes  up  water 
and  oxygen,  forming  allantoin  and  carbonic  acid  : 

2C5H,N,0,  +  2H.,0  +  O2  =  2C\HgN,0,  +  2CO,. 
Uric  acid.  Allantoin. 

The  allantoin  crystallizes  out  in  about  twenty-four  hours.  By 
subjecting  allantoin  to  the  action  of  baryta  water,  hydrolysis 
and  oxidation  again  take  place,  and  urea  and  oxalic  acid  are 
formed  : 

2C,HgNp3  ^  4H,0  +  O.,  =  4CON2H^  -f  2C2HJO,. 

Allantoin.  Urea.  Oxalic  acid. 

5.  The  following  decompositions  are  interesting,  as  the 
murexide  test  is  the  chief  characteristic  test  for  uric  acid. 

By  oxidation  with  nitric  acid,  alloxan  and  urea  are  formed : 

2C5H^Np3+2H20+02  =  2C4H2N2O,  -u  2C0N,H,. 

By  heating  or  by  electrolysis,  alloxan  splits  into  alloxantin, 
parabanic  acid,  and  carbonic  acid  : 

3C,H,N.p,  =  C«H,N,0,  +  C3H.,N,03  +  CO, ; 

Alloxan.  Alloxantin.        Parabanic 

acid. 

and  on  treating  alloxantin  with  ammonia  the  purple  color  due 
to  murexide  or  purpurate  of  anmionia  appears: 

C,H,N,0,  +  2NH3  =  CgH^N.O,  +  H,0. 
Alloxantin.  Murexide. 

Since  uric  acid  exi.st.s  in  combination  as  urates,  it  is  not 
ordinan'l)'  found  in   a  free  state.      It  may,  however,  be  de- 


URIC  ACID. 


63 


posited  in  the  urine  in  crystalline  form,  either  while  in  the 
body  or  after  the  urine  has  been  voided.  It  may  then  be 
seen  as  a  deposit  of  minute  reddish  crystals,  or,  more 
rarely,  as  reddish  sand  or  gravel. 

Uric  acid  crystallizes  in  the  form  of  yellow  or  yellowish- 
red  crystals  of  a  variety  of  shapes — -rhombic  and  rectangular 
prisms,  whetstone-,  barrel-,  wedge-,  club-,  diamond-shaped, 
and  as  rosettes.  (Plate  3.)  The  diamond-shaped  ciystals 
usually  either  have  a  very  faint  yellow  tint  or  are,  not  in- 
frequently, perfectly  colorless. 

Crystals  of  uric  acid  and  those  of  its  salt, — ammonium 
urate, — together  with   those   of  hippuric   acid  and   leucin, 


Fig.  7. — Uric  acid  and  urates  (Funke). 


constitute  the  only  crystalline  sediments  of  the  urine  col- 
ored yellow  or  yellowish-red. 

There  are  certain  conditions  of  the  body  in  which,  as  a 
result  of  overfeeding  and  consequent  sedentary  habits,  and 
in  some  cases  from  hereditary  influences,  the  oxidation 
changes  in  the  body  are  lessened,  and  uric  and  oxalic  acids 
are  formed  in  greater  proportion  to  urea  than  under  normal 
conditions. 

Where  is  Uric  Acid  Formed  ? — Two  different  views  upon 
this  subject  have  been  advanced  :  ( i )  That  it  is  formed  in  the 
tissues,  especially  in  the  liver  and  spleen,  and  merely  ex- 
creted by  the  kidneys  ;  (2)  that  the  kidneys  not  only  excrete, 
but  also  constitute  the  seat  of  formation  of,  uric  acid.      The 


64  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

former  view  (i)  is  most  generally  held,  and  is  supported  by 
the  following  facts  :  [a)  Under  normal  conditions  uric  acid 
is  found  in  traces  in  the  blood.  ((^)  After  extirpation  of 
the  kidneys  it  continues  to  be  formed,  (c)  The  secretion 
of  uric  acid  is  greatest  during  the  period  of  digestion — that 
is,  at  a  time  when  the  liver  and  spleen  are  most  active,  (d) 
In  gout  and  in  anemic  conditions,  ^  where  the  excretion  of 
uric  acid  is  diminished,  it  accumulates  in  the  blood  and  tissues. 

The  chief  advocate  of  the  second  view  (2)  is  Garrod,  who 
bases  his  conclusions  on  the  fact  of  the  small  amount  of  uric 
acid  in  the  blood  of  reptiles,  and  also  on  the  fact  that  he 
was  unable  to  find  a  larger  quantity  of  uric  acid  in  the 
liver  and  spleen  of  birds  than  in  those  organs  in  mammals. 

Horbaczewski  ^  claims  that  uric  acid  is  formed  as  a  re- 
sult of  the  disintegration  of  the  tissues  containing  nuclein, 
especially  the  leucocytes  ;  that  the  amount  of  uric  acid 
excreted  increases  when  the  number  of  leucocytes  in  the 
blood  is  increased.  He  also  claims  that  this  is  the  explana- 
tion of  the  large  amount  of  uric  acid  in  the  urine  of  chil- 
dren, especially  the  new-born,  the  small  amount  in  hunger, 
and  the  larger  quantity  following  the  ingestion  of  a  meat  diet. 

The  investigations  of  Schroder  ^  and  Minkowski  "*  justify 
the  conclusion  that  uric  acid  is  formed  chiefly  in  the  liver, 
where  it  appears  as  a  result  of  the  synthesis  of  ammonia 
and  lactic  acid,  which,  after  the  removal  of  the  liver,  and 
also  in  extensive  degenerative  changes  of  this  organ  (cirrho- 
sis, acute  yellow  atrophy,  etc.),  appear  in  the  urine  in  equiv- 
alent quantities.  Further,  that  small  quantities  of  uric  acid 
following  extirpation  of  the  liver  are  formed  from  xanthin 
and  similar  substances. 

The  quantity  of  uric  acid  eliminated  in  twenty -four  hours 
under  normal  conditions  ranges  between  0.2  and  i  gram,  the 
average  being  about  o.  5  gram.  According  to  Neubauer  and 
Vogel,^  the  twenty-four-hour  quantity  may,  normally,  go  as 
high  as  1.25  grams.  In  rare  instances,  especially  in  disease, 
the  total  quantity  of  uric  acid  may  exceed  this  figure.  The 
proportion  of  uric  acid  to  urea  is  normally  about  as  i  :  45. 

The  quantity  of  uric  acid  in  the  urine  is  not  necessarily 
excessive  when  a  deposit  of  uric  acid  crystals  takes  place 

^  Von  Jaksch,  *' Deutsche  med.  Wochenschr.,"  1890,  No.  23. 
2  "  Monatsh.  f.  Chemie,"  Bd.  xn,  232,  189I. 
»  "  Lud wig's  Festschrift,"  1887,  S.  89.  *  Loc.  cit. 

5  "Analyse  des  Hams,"  Bd.  i,  1898,  S.  312. 


Pl.ATK    3 


Uric-acid  Crystals  ;  Normal  Color  (after  Peyer). 


URIC  ACID.  65 

in  the  urine  upon  cooling.  As  a  matter  of  fact,  such  a  de- 
posit may,  and  very  often  does,  occur  when  the  quantity 
of  uric  acid  is  both  relatively  and  absolutely  diminished. 
The  separation  of  uric  acid  cr^'stals  from  the  urine  is 
usually  dependent  upon  one  of  three  conditions  : 

1.  A  high  degree  of  concentration  of  the  urine,  too 
little  water  being  present  to  keep  the  uric  acid  in  solution. 

2.  Marked  acidity  of  the  urine,  the  salts  of  uric  acid 
being  deprived  of  a  part  of  the  alkali ;  the  larger  the  pro- 
portion of  alkali  combined  with  the  uric  acid,  the  more 
soluble  it  becomes. 

3.  A  high  percentage  of  uric  acid.  Any  condition 
that  results  in  an  increased  formation  of  uric  acid  in  the 
body  causes  its  increase  in  the  blood,  and  hence  an 
increased  amount  in  the  urine,  with,  usually,  a  resulting 
deposition  of  the  crystals. 

When  urine  habitually  contains  a  deposit  of  uric  acid,  an 
alkali  or  some  substance  with  which  the  uric  acid  will  com- 
bine should  be  administered,  in  order  to  prevent  an  irrita- 
tion or  inflammation  of  the  urinary  tract  by  the  crystals. 

In  the  consideration  which  follows  the  writer  refers  to  the 
uric  acid  in  solution  (as  urates)  and  not  to  a  deposit  of  uric 
acid  crystals. 

Clinical  Significance. — Uric  acid  is  absolutely  in- 
creased (i)  by  an  abundant  meat  diet,  especially  when 
combined  with  a  limited  amount  of  outdoor  exercise  :  in 
other  words,  increased  metabolism  together  with  limited 
oxidation.  (2)  In  most  of  the  acute  diseases.  (3)  In 
acute  diseases  of  the  lung,  as  in  pneumonia,  or  by  any  dis- 
ease that  interferes  with  respiration,  as  hydrothorax  and 
pneumothorax,  also  by  the  upward  pressure  of  abdominal 
tumors,  marked  ascites,  etc.  (4)  In  chronic  heart  disease 
or  in  any  condition  that  interferes  with  the  circulation.  (5) 
In  liver  disease.  (6)  In  disease  of  the  spleen.  (7)  In  vari- 
ous forms  of  anemia,  especially  splenic  leukemia,  in  which 
case  the  proportion  of  uric  acid  to  urea  may  be  as  high  as 
I  :  15,  or  even  more.  (8)  In  gout  folloiving  the  par- 
oxysm. (9)  In  diabetes  mellitus.  ^  (10)  Following  the 
administration  of  nuclein.^ 

^  The  question  as  to  whether  uric  acid  is  actually  increased  in  diabetes 
mellitus  has  given  rise  to  much  controversy.  It  is  probable  that  the  increase, 
if  any,  is  not  marked. 

2  "  Monatsh.  f.  Chemie,"  Bd.   xil,  234,  1891, 
S 


66  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

Uric  acid  is  absolutely  diminished  (i)  by  low  nitrog- 
enous diet.  (2)  By  the  habitual  ingestion  of  large  quan- 
tities of  water  (long-continued  use).  (3)  In  most  forms  of 
advanced  disease  of  the  kidneys.  (4)  In  gout  during  the 
paroxysm.  (5)  Following  the  administration  of  large 
doses  of  quinine.  (6)  In  most  of  the  general  chronic  dis- 
eases. 

Detection. — i.  The  Murexide  Test. — A  small  portion 
of  urinary  sediment  is  evaporated  to  dryness  on  a  porcelain 
plate  or  capsule,  and  a  drop  or  two  of  nitric  acid  is  added  to 
dissolve  it.  The  mixture  is  then  stirred  thoroughly  with 
a  glass  rod,  and  carefully  evaporated  to  dryness  over  a 
spirit  or  a  small  Bunsen  flame.  When  dry  and  cool,  add 
one  or  two  drops  of  ammonic  hydrate,  and  if  uric  acid 
or  urates  are  present,  a  beautiful  purple-red  color  promptly 
appears,  gradually  diffusing  itself  over  the  bottom  of  the 
plate  or  capsule  as  the  ammonia  spreads. 

2.  Strongly  acidulate  the  urine  with  concentrated  hydro- 
chloric acid,  and  allow  the  mixture  to  stand  from  eighteen 
to  twenty-four  hours.  Usually,  a  deposit  of  uric  acid  crys- 
tals appears. 

3.  Uric  acid  may  be  detected  in  the  urine  and  other 
fluids,  when  traces  of  the  acid  or  of  urates  are  present,  by 
a  method  suggested  by  Garrod.  A  small  portion  of  the 
suspected  fluid  is  treated  on  a  watch-glass  with  a  few  drops 
of  glacial  acetic  acid.  A  few  filaments  of  tow  or  very  thin 
silk  are  placed  in  the  mixture,  and  the  whole  is  set  aside 
under  a  bell-jar  in  a  warm  place  for  from  twenty -four 
to  forty-eight  hours.  Gradually,  crystals  of  uric  acid  sepa- 
rate and  are  deposited  upon  the  filaments.  Their  character 
may  be  readily  recognized  by  microscopic  examination. 

4.  When  a  solution  of  uric  acid  or  of  a  urate  is  boiled 
with  an  alkaline  solution  of  copper  (Fehling's  solution),  a 
yellowish-red  or  reddish  precipitate  of  suboxide  of  copper 
occurs. 

Quantitative  Determination  of  Uric  Acid. — Heintz's 
Method. — Take  200  c.c.  of  filtered  urine  that  is  free  from 
albumin,  and  add  10  c.c.  of  concentrated  hydrochloric  acid. 
Let  this  stand  for  twenty-four  hours  in  a  cool  place,  then 
collect  the  separated  uric  acid  crystals  on  a  previously  dried 
and  weighed  filter-paper,  and  wash  once  or  twice  with  cold 
distilled  water.  Dry  the  filter-paper  holding  the  uric  acid 
crystals  at  about  100°  C;  cool  and  weigh.     By  subtracting 


URIC  ACID.  67 

the  weight  of  the  filter-paper,  the  result  will  be  the  weight 
of  the  uric  acid  in  200  c.c.  of  urine. 

This  process  can  be  considered  only  approximate,  and 
should  not  be  relied  upon  for  accurate  results.  It  fre- 
quently happens  that  urines  containing  uric  acid  do  not  give 
a  precipitate  by  this  method  ;  it  then  becomes  necessary  to 
employ  other  longer  and,  probably,  more  accurate  methods. 

Fokker-Salkowski  Method.^ — Of  the  several  gravi- 
metric methods  which  have  been  suggested,  this  is  perhaps 
the  most  reliable.  It  depends  upon  the  precipitation  of 
uric  acid  as  ammonium  urate,  which,  on  account  of  its  diffi- 
cult solubility,  can  be  easily  handled,  and  with  compara- 
tively little  loss. 

Process. — Take  200  c.c.  of  urine,  render  alkaline  with  20 
c.c.  of  sodic  hydrate,  allow  it  to  stand  an  hour,  and  to  the 
filtered  mixture  add  10  c.c.  of  a  solution  of  ammonium 
chloride  (i  :  5).  Let  this  stand  for  forty-eight  hours. 
Transfer  the  precipitate  to  a  previously  dried  and  weighed 
filter-paper,  and  wash  two  or  three  times  with  distilled 
water.  Then  treat  the  precipitate  several  times  with  dilute 
hydrochloric  acid  (i  :  10)  until  all  of  the  ammonium  urate 
has  been  decomposed.  This  leaves  on  the  filter  all  of  the 
uric  acid  except  what  has  been  dissolved  and  carried 
through  into  the  filtrate.  This  filtrate  is,  therefore,  saved 
and  allowed  to  stand  six  hours,  after  which  any  separated 
uric  acid  crystals  are  thrown  on  to  the  weighed  filter-paper. 
The  precipitate,  which  represents  the  total  uric  acid  in  200 
c.c.  of  urine,  is  washed  twice  with  water  (30  c.c),  then  with 
alcohol  until  the  acid  reaction  has  disappeared,  and  finally 
the  filter-paper  is  dried  and  weighed.  The  difference  in 
weight  plus  0.03  gram  (correction  for  solubility)  gives  the 
quantity  of  uric  acid  in  200  c.c.  of  urine.  From  this  cal- 
culate the  amount  for  twenty -four  hours. 

If  the  urine  is  dilute,  it  should  be  concentrated  so  as  to 
have  a  specific  gravity  of  from  1017  to  1020  before  the  fore- 
going test  is  applied.  The  presence  of  albumin  in  the  urine 
does  not  interfere  with  the  test. 

Hopkin's  Method. — In  this  process  the  uric  acid  and  all 
of  the  urates  are  precipitated  by  saturating  the  urine  with 
ammonium  chloride,  which  converts  all  into  ammonium 
urate.    This  is  then  filtered  out,  and  the  uric  acid  separated 

1  "  Pfliiger's  Archiv,"  Bd.  X,  157,  1875  ;  "  Virchow's  Archiv,"  Bd.  LXVIII, 
401,  1876. 


68  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

by  the  action  of  hydrochloric  acid.  The  final  estimation 
is  then  made  by  titrating  with  a  standard  solution  of  potas- 
sium permanganate,  which  Hopkins  has  found  to  be  more 
accurate  than  weighing.  Exceedingly  accurate  results  are 
claimed  for  this  process,  and  it  has  the  advantage  of  being 
conducted  with  ease  and  comparative  rapidity. 

The  following  solution  is  required  :  A  twcnticth-nonnal 
sobition  of  potassium  pcnnangaiiatc.  This  solution  is  pre- 
pared by  dissolving  1.577  grams  of  pure  crystals  of  potas- 
sium permanganate  in  about  900  c.c.  of  distilled  water.  A 
portion  of  this  solution  is  then  placed  in  a  burette  and 
titrated  against  a  decinormal  solution  of  oxalic  acid  as  fol- 
lows :  Take  10  c.c.  of  the  decinormal  oxalic  acid  solution 
in  a  beaker,  add  some  dilute  sulphuric  acid,  and  heat  this 
mixture  to  60°  C.  To  this  hot  mixture  add  the  solution 
of  potassium  permanganate  until  a  faint  but  permanent  pink 
color  is  produced.  Note  the  number  of  cubic  centimeters 
of  the  permanganate  solution  used,  and  then  dilute  the 
remainder  so  that  20  c.c.  of  it  will  exactly  correspond  to 
10  c.c.  of  the  decinormal  solution  of  oxalic  acid. 

Each  cubic  centimeter  of  the  twentieth-normal  solution 
of  potassium  permanganate  corresponds  to  0.00375  gram  of 
uric  acid. 

The  permanganate  solution  will  usually  retain  its  strength 
for  several  weeks,  but  it  should  always  be  restandardized 
by  titration  with  oxalic  acid  before  it  is  used. 

The  process,  as  applied  to  all  urines,  normal  and  patho- 
logic, is  as  follows  : 

I.  In  Normal  Urine  zvithont  Deposit. — [a)  To  100  c.c. 
of  the  urine  is  added  ammonium  chloride  until  practically 
saturated  ;  about  3  5  grams  are  necessary.  When  a  small 
quantity  of  the  chloride  remains  undissolved,  even  after 
brisk  stirring  at  intervals  of  a  few  minutes,  saturation 
is  nearly  complete.  As  the  temperature  of  the  urine  again 
rises,  from  the  depression  due  to  the  process  of  solution, 
any  residual  crystals  will,  for  the  most  part,  dissolve  ;  but 
there  is  no  necessity  for  adding  more. 

{b)  After  having  stood  for  two  hours  or  longer, — better 
with  occasional  agitation  to  promote  subsidence, — the  pre- 
cipitate produced  is  filtered  through  a  thin  filter-paper, 
and  washed  three  or  four  times  with  a  saturated  solution 
of  ammonium  chloride.  The  filtrate  should  remain  per- 
fectly clear. 


URIC  ACID.  69 

(c)  With  a  jet  of  hot  distilled  water  the  urate,  which  will 
be  somewhat  pigmented,  is  now  washed  off  the  filter  into  a 
small  beaker,  and  heated  just  to  boiling  with  an  excess  of 
hydrochloric  acid.  It  is  then  allowed  to  stand,  in  order 
that  the  uric  acid  may  separate  completely.  Two  hours  are 
sufficient  if  the  liquid  be  cooled.  The  acid  is  then  filtered 
off  and  washed  with  cold  distilled  water.  The  filtrate 
should  be  measured  before  the  washing  is  begun,  and  one 
milligram  added  to  the  final  result  for  each  15  c.c.  of  liquid 
present.      This  need  never  be  more  than  from  20  to  30  c.c. 

{li)  The  acid  is  now  again  washed  off  the  filter  with  hot 
water,  sodium  carbonate  is  added,  it  is  warmed  until  dis- 
solved, and  the  solution  then  made  up  to  100  c.c.  Being 
transferred  to  a  flask  of  sufficient  capacity,  it  is  mixed  with 
20  c.c.  of  concentrated  pure  sulphuric  acid,  and  immediately 
titrated  with  the  twentieth-normal  potassium  permanganate 
solution.  The  latter  should  be  added  slowly  toward  the 
end  of  the  reaction,  the  close  of  which  is  marked  by  the  first 
approach  of  a  pink  color,  which  is  permanent  for  an  appre- 
ciable interval.  The  flask  should  be  agitated  throughout 
the  titration. 

Since  each  cubic  centimeter  of  the  potassium  perman- 
ganate solution  is  equal  to  0.00375  gram  of  uric  acid,  the 
number  of  cubic  centimeters  of  permanganate  solution  multi- 
plied by  0.00375,  P^us  the  correction  of  one  milligram  for 
each  15  c.c.  of  liquid  present,  will  give  the  amount  of  uric 
acid  in  the  100  c.c.  of  urine  used.  From  this  the  quantity 
of  uric  acid  in  the  twenty-four-hour  urine  can  be  readily 
calculated. 

2.  Acid  Urines  Containing  Cystin. — The  author  recom- 
mends the  addition  of  a  small  amount  of  amnionic  lu'drate  ; 
heat  and  filter.  The  ammonium  chloride  may  be  added 
while  the  urine  is  still  warm. 

J.  Alkaline  Urines  ivitli  an  Abundant  Deposit  of  Phos- 
phates.— Filter  off  the  phosphates  after  complete  precipita- 
tion by  heat.  The  ammonium  urate  separates  more  rapidly 
in  alkaline  than  in  acid  urine.  The  only  objection  to  adding 
ammonic  hydrate  in  all  cases  is  its  tendency  to  precipitate 
the  phosphates. 

4.  Albuminous  Urines. — Albumin  does  not  interfere  with 
the  accurate  determination  of  uric  acid  by  this  method,  but 
requires  a  little  longer  digestion  with  an  excess  of  hydro- 
chloric acid,  in  order  to  form  the  soluble  acid-albumin. 


70  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

5.  HigJily  Pigvioited  Urhw. — The  pigment  should  be 
removed  from  the  urate  precipitate  by  treating  thoroughly 
with  alcohol,  and  after  acidulation  the  filtrate  is  gradually 
heated  to  boiling  and  then  digested  for  some  time  on  a 
water-bath.  The  separated  crystals  are  then  thoroughly 
washed. 

In  a  urine  containing  bile  the  biliary  pigment  may  come 
down  in  considerable  quantity  ;  but  despite  this,  the  ultimate 
error  is  small. 

Folin's  Method.^ — This  process  depends  upon  the  pre- 
cipitation of  uric  acid  as  ammonium  urate,  by  means  of 
ammonium  sulphate,  and  is  conducted  as  follows  : 

Process. — To  100  c.c.  of  filtered  urine  add  10  grams  of 
ammonium  sulphate  ;  allow  it  to  stand  two  hours,  filter, 
and  wash  the  urate  precipitate  with  a  ten  per  cent,  solution 
of  ammonium  sulphate  until  it  is  free  from  chlorine.  Dis- 
solve the  entire  urate  precipitate  in  hot  distilled  water,  add 
to  this  solution  i  5  c.c.  of  concentrated  sulphuric  acid,  and 
then  titrate,  while  hot,  with  a  twentieth-normal  solution  of 
potassium  permanganate,  each  cubic  centimeter  of  which 
corresponds  to  0.00375  gram  of  uric  acid.  Read  off  the 
number  of  cubic  centimeters  of  permanganate  solution 
used,  multiply  by  0.00375,  and  to  the  result  add  one  milli- 
gram for  correction.  This  equals  the  amount  of  uric  acid 
in  100  c.c.  of  urine.  From  this  calculate  the  quantity  for 
twenty-four  hours. 

According  to  Hofmeister,-  neither  albumin  nor  globu- 
lin are  precipitated  by  a  ten  per  cent,  solution  of  ammonium 
sulphate. 

Quantitative  Estimation  of  Uric  Acid  by  the  Centri- 
fuge.— The  following  method,  devised  by  Dr.  R.  Harvey 
Cook,^  promises  excellent  results  and  has  the  advantages  of 
being  rapid  and  quite  accurate.  It  is  based,  chemically, 
on  the  method  of  Haycraft,  in  that  the  uric  acid  is  pre- 
cipitated as  urate  of  silver. 

The  follow'ing  apparatus  are  necessary  :  a  centrifuge,  four 
graduated  tubes  of  a  capacity  of  15  c.c.  each,  and  a  pipette 
holding  one  cubic  centimeter. 

Process. — Place  10  c.c.  of  urine  in  the  graduated  tubes, 
add  to  this  from  0.5  to  i  gram  of  crystals  of  sodium  car- 

^  "Zeitschr.  f.  physiol.  Chemie,"  Bd.  xxiv,  3,  S.  224. 

2  "  Archiv  f.  exp.  Pathol,  u.  Pharm.,"  Bd.  XXV,  247,  1888. 

3  "  Medical  Record,"  March  12,  1898,  p.  373. 


XANTHIN  BASES.  71 

bonate,  and  i  or  2  c.c.  of  ammonium  hydrate.  Shake 
until  the  sodium  carbonate  is  dissolved;  this  precipitates 
the  earthy  phosphates.  Separate  this  precipitate  in  the 
centrifuge,  and  decant  all  of  the  supernatant  clear  urine 
into  another  graduated  tube.  To  the  clear  urine,  now 
free  from  phosphates,  add  2  c.c.  of  ammonic  hydrate  and 
2  c.c.  of  an  ammoniacal  solution  of  silver  nitrate  made  by 
dissolving  5  grams  of  silver  nitrate  in  100  c.c.  of  distilled 
water,  and  adding  ammonic  hydrate  until  the  solution  be- 
comes clear. 

The  addition  of  the  silver  solution  causes  the  uric  acid  to 
be  precipitated  as  the  urate  of  silver — a  translucent,  slimy 
substance.  Separate  this  precipitate  in  the  centrifuge,  pour 
off  the  supernatant  urine,  and  add  to  the  precipitate  an 
excess  of  ammonic  hydrate — at  least  5  c.c. — and  mix  thor- 
oughly. By  this  last  step  any  of  the  chlorides  that  may 
have  been  precipitated  are  redissolved,  leaving  only  pure 
urate  of  silver.  Lastly,  centrifugalize  again  until  the  silver 
urate  precipitate  has  fallen  as  low  as  it  will  go. 

Each  3V  <^^  ^  ^^^^^  centimeter  as  marked  on  the  gradu- 
ated tube  is  equivalent  to  0.00 1 176  gram  of  uric  acid  in  10 
c.c.  of  urine.  For  example  :  if  0.5  be  the  lowest  reading 
obtainable,  then  5  X  0.001176  =  0.00588  gram  of  uric 
acid  in  10  c.c.  of  urine.  In  order  to  obtain  the  per- 
centage, multiply  this  result  by  10  ;  if  the  twenty-four- 
hour  quantity  of  urine  be  known,  the  total  uric  acid  can  be 
easily  calculated. 

XANTHIN  BASES. 

•A  number  of  xanthin  bases  have  been  found  in  urine  : 
Xanthin,  C.H.N.O^ ;  Heteroxanthin,  CgHgN^ ;  Paraxan- 
thin,  C.HgNp, ;  Guanin,  C.H,Np  ;  Hypoxanthin  (sarkin), 
QH.Np  ;  Adenin,  CH.N, ;  Episarkin,  C.HgN,©  ;  Carnin, 
qHsNPj;  Epiguanin,  Ci^Hj^NgO^ ;  and,  finally,  an  un- 
known base  discovered  by  Kriiger. 

The  xanthin  bases  have  also  been  called  nuclein  bases  (Kos- 
sel)  and  alloxur  bases  (Kossel  and  Kriiger).  The  alloxur  bases, 
together  with  uric  acid,  have  been  given  the  names  alloxur 
bodies  (Kossel  and  Kruger)  and  purin  bodies  (E.  Fischer). 

Kruger  and  Salomon  ^  have  recently  made  an  extensive  study 
of  the  alloxur  bases.     From  10,000  liters  of  urine  they  obtained 

1  "Zeitschr.  f.  physiol.  Chemie,"  Bd.  xxvi,  1898,  S.  350. 


72 


ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 


the  following:  Xanthin,  lo.ii  gm.;  heteroxanthin,  22.345 
gm.;  l-methylxanthin,  31.285  gm.;  paraxanthin,  15.31  gm.; 
hypoxanthin,  8.50  gm.;  adenin,  3.54  gm.;  and  epiguanin, 
3.4  gm.  The  bases  adenin,  hypoxanthin,  and  xanthin,  due 
to  the  breaking  down  of  nuclein,  occur  in  smaller  quantities 
than  the  homologues  of  xanthin  which  are  probably  derived 
from  the  theobromin,  caffein,  and  theophyllin  introduced  into 
the  system  by  the  use  of  tea  and  coffee,  paraxanthin  being 
obtained  from  caffein,  heteroxanthin  from  theobromin,  and 
l-methylxanthin  from  theophyllin. 

A  brief  consideration  of  the  most  important  of  the 
xanthin  bases  follows.^ 

Xanthin  (QH^N^O,). — When  pure  xanthin  is  dissolved 
in  a  weak  alkali   with   the  aid  of  heat,    strongly  diluted 


pig._  g. — Xanthin  crystals  (after  the  drawings  of   Horbaczewski,  as  represented  in 
Neubauer  and  Vogel). 


(i  :  2000),  and  then  saturated  with  acetic  acid,  it  crystallizes 
in  macroscopic,  colorless,  glistening,  rhombic  plates,  ar- 
ranged in  groups.  (Fig.  8.)  Xanthin,  which  is  separated 
from  its  concentrated  aqueous  solution  by  boiling,  is  amor- 
phous, but  on  standing  soon  collects  in  flakes,  films,  or  crusts. 
Xanthin  is  soluble  in  13,000  to  14,000  parts  of  cold 
water,  and  in  1300  to  1400  parts  of  hot  water;  it  is  diffi- 
cultly soluble  in  dilute  alcohol  and  dilute  acids,  but  much 
more  soluble  in  amnionic  hydrate  than  in  water.  On 
cooling,  xanthin  separates  from  its  warm  saturated  solution 

1  For  details  see  Neubauer  and  Vogel,  Bd.  I,  1898,  S.  331. 


HETEROXANTHIN.  73 

in  ten  per  cent,  ammonia  in  the  form  of  fine  needles  of 
xanthin-ammonium.  If  xanthin  be  dissolved  in  very  weak 
sodic  hydrate,  on  standing  small  crystals  of  xanthin-sodium, 
CjHgNaN^Og  .  H.,0,  separate.  A  solution  of  xanthin 
in  ammonia  gives,  with  an  ammoniacal  solution  of  zinc 
chloride,  a  white  precipitate  which  is  soluble  in  an  excess 
of  ammonia.  Xanthin  in  crystalline  form  contains  one 
molecule  of  water  of  crystallization  ;  when  amorphous,  it  is 
water-free.  If  xanthin  is  heated  in  a  closed  tube,  it  sub- 
limes without  melting,  and  results  in  a  decomposition  with 
the  evolution  of  hydrocyanic  acid. 

Xanthin  is  a  constituent  of  normal  urine,  but  is  present 
only  in  traces.  Kriiger  and  Salomon  ^  found  only  13  grams 
in  10,000  liters  of  normal  human  urine.  Stadthagen  was 
able  to  isolate  from  the  twenty-four-hour  quantity  of  urine 
of  a  healthy  individual  on  a  mixed  diet  0.032  and  0.025 
gram. 

Xanthin  contains  one  atom  less  of  oxygen  than  uric  acid, 
to  which  it  is  closely  allied.  It  has  rarely  been  encountered 
as  a  constituent  of  the  urinary  sediment.  It  has  been  found 
as  a  constituent  of  a  very  rare  form  of  calculus,  and  in  those 
cases  reported,  was  always  observed  in  children. 

Xanthin  is  increased  in  leukemia  (as  high  as  0.028  gram 
in  100  c.c.) ;  Stadthagen  found  0.07  gram  in  the  twenty-four- 
hour  urine  as  an  average  of  seven  determinations.  Pouchet^ 
found  it  in  unusual  quantities  in  fever,  and  particularly  in 
affections  of  the  nervous  system — pachymeningitis  cervicalis 
hypertrophica  and  tabes  dorsalis. 

Detection. — (i)  When  a  solution  of  xanthin  in  a  fixed 
alkali  is  added  to  sodium  or  calcium  hypochlorite,  nitrogen 
gas  is  evolved  and  the  solution  becomes  green,  changing  to 
a  brown  and  finally  to  a  yellow.  (2)  When  xanthin  is 
heated  to  200°  C.  with  fuming  hydrochloric  acid,  it  is  de- 
composed into  glycocoll,  ammonia,  carbonic  acid,  and  formic 
acid.  (3)  When  evaporated  to  dryness  with  nitric  acid,  a 
yellow  residue  remains,  which  becomes  violet  on  the  addi- 
tion of  potassium  hydrate,  the  violet  color  increasing  upon 
the  application  of  heat.     (See  Murexide  Test  for  Uric  Add.) 

Heteroxanthin  (C.HgNp,  .  CH3).  —  Heteroxanthin, 
when   pure,    crystallizes    from   its    hot  aqueous  solution  in 

i"Zeitschr.  f.  physiol.  Chemie,"  Bd.  xxi,  169,  1895. 
2  "Thesis,"  Paris,  1880. 


74  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

glossy  needles  about  a  half  centimeter  in  length,  also  in 
thorn-like  spheres,  and  in  thick  columns  which  have  a  fan- 
like arrangement.  It  is  soluble  in  1592  parts  of  water  at 
18°  C,  in  109  parts  of  boiling  water,  and  is  sparingly 
soluble  in  absolute  alcohol.  When  pure,  it  is  insoluble  in 
ether  and  chloroform  ;  but  when  impure,  it  is  sparingly 
soluble  in  chloroform.  It  is  readily  soluble  in  ammonia  and 
other  alkalies.  Heteroxanthin  combines  with  sodium  to 
form  a  double  salt,  prepared  by  the  addition  of  sodic  hydrate 
to  its  concentrated  solution. 

Heteroxanthin  is  a  constituent  of  normal  urine,  but  is 
present  only  in  minute  quantities.  Salomon  found  only  i 
gram  in  looo  liters ;  Kriiger  and  Salomon  isolated  7.5 
gram  from  10,000  liters  of  normal  human  urine. 

Clinically,  it  is  increased  in  leukemia,  in  phosphorus- 
poisoning,  and  following  the  ingestion  of  theobromin  and 
caffein. 

Detection. — Heteroxanthin  does  not  respond  to  the 
tests  for  xanthin.  It  gives  an  intense  Weidel's  reaction 
with  hydrochloric  acid  and  a  trace  of  potassium  chlorate  ; 
the  red  residue  changes  to  a  violet  on  the  addition  of  potas- 
sium hydrate. 

Hypoxanthin  (C.H^N^O). — Hypoxanthin,  also  termed 
sarkin,  is  present  in  normal  urine,  but  only  in  minute  quan- 
tities. Pure  hypoxanthin  does  not  crystallize  in  the  form  of 
needles,  but  always  appears  on  the  bottom  and  sides  of  the 
glass  or  on  the  surface  of  the  fluid  in  the  form  of  a  film,  as 
oval  kernels  with  sharp  angles.  Like  xanthin  and  hetero- 
xanthin, when  heated  in  a  closed  tube  it  sublimes  and 
evolves  hydrocyanic  acid.  It  is  soluble  in  300  parts  of  cold 
water  and  in  78  parts  of  hot  water,  also  in  900  parts  of  hot 
alcohol.  It  is  more  readily  soluble  in  ammonia  than  in 
water.  It  is  not  precipitated  by  saturating  its  solution  with 
ammonium  chloride.  Hypoxanthin  is  precipitated  from  its 
solution  in  alkalies  by  carbonic  acid.  It  combines  with 
the  salts  of  sodium,  zinc,  and  calcium  to  form  double 
salts. 

Hypoxanthin  has  been  found  in  the  normal  urine  of  man 
by  Salomon,  Salkowski,  and  others.  It  is  most  abundant 
after  a  hearty  meat  diet  (in  dogs).  It  appears  to  be  in 
larger  quantities  in  the  urine  of  leukemia  than  in  that  of 
health  (Stadthagen  isolated  an  average  quantity  of  0.009 
gram — as   high  as  0.027  gram — from  leukemic  urine),  also 


PARAXANTHIN.  75 

in  diseases  of  the  liver  and  kidneys  (Thudichum),  and  in 
fever  and  diseases  of  the  central  nervous  system  (Pouchet). 

Detection. — When  hypoxanthin  is  treated  with  zinc 
and  dikite  hydrochloric  acid,  and  then  sodic  hydrate  is 
added,  a  red  or  reddish-brown  color  appears,  the  result  of 
the  absorption  of  oxygen  from  the  air.  Hypoxanthin  does 
not  give  a  green  color  with  sodic  hydrate  and  calcium 
hypochlorite  as  does  xanthin. 

Paraxanthin  (C5H.,Np^(CH3y.— Paraxanthin  is  iso- 
meric with  theobromin  and  theophyllin.  It  crystallizes 
in  colorless,  glossy,  six-sided  plates.  It  is  difficultly  solu- 
ble in  cold  water,  but  dissolves  much  more  readily  in  hot 
water,  its  solutions  having  a  neutral  reaction.  It  is  insolu- 
ble in  alcohol  and  ether.  It  combines  with  sodium  to  form 
a  double  salt,  which  has  much  the  same  general  properties 
as  the  compound  of  sodium  with  heteroxanthin. 

Paraxanthin  has  been  detected  in  the  urine  of  man  by 
Thudichum  and  Salomon.  Like  the  other  bases  of  this 
group,  it  was  found  in  unusual  quantities  in  leukemic  urines. 
Comparatively  little  is  known  of  the  clinical  significance 
of  this  substance. 

Detection. — Paraxanthin  gives  the  Widal  reaction,  but 
does  not  respond  to  the  tests  for  xanthin. 

The  isolation  of  the  xanthin  bases  is  accomplished  in  four 
ways:  (i)  Precipitation  with  ammoniacal  solution  of  silver 
nitrate  ;  (2)  with  copper  suboxide  ;  (3)  with  phosphotungstic 
acid  ;   (4)  with  cupric  acetate.  ^ 


NUCLEIC  AQD. 

This  acid  has  been  found  by  Morner  in  very  small 
quantities  in  the  urine.  It  appears,  however,  in  large 
amounts  in  combination  with  albumin  as  nucleo-albumin. 
(See  p.  140.)  The  nucleic  acids  are  compounds  of  phos- 
phoric acid,  xanthin  bases,  and  a  nitrogen-free  substance. 
Some  of  these  compounds  have  been  recognized  as  pentose 
and  hexose.  The  amount  of  phosphorus  in  the  nucleic 
acids  varies,  but  may  reach  as  high  as  9  or  10  per  cent. 
They  zx^  amorphous,  have  an  acid  reaction,  are  soluble  in 
ammonia,  in  alkaline  hydrates,  or  in  distilled  water  holding 
a  small   amount  of  alkali,  and  are  precipitated  from  their 

'  See  Neubauer  and  Vogel,  "Analyse  des  Hams,"  Bd.  i,  1898,  S.  362. 


76  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

solutions  by  a  small  amount  of  hydrochloric  acid,  but 
not  by  acetic  acid.  They  are,  however,  precipitated  by  an 
excess  of  glacial  acetic  acid.  They  are  completely  precipi- 
tated by  alcohol  in  the  presence  of  hydrochloric  acid.  Ac- 
cording to  Kutscher,  nuclein  is  precipitated  from  a  neutral 
solution  of  the  salts  of  nucleic  acid  by  an  aqueous  solution 
of  albumose.  Noll  ^  has  recently  succeeded  in  forming 
levulinic  acid  from  nucleic  acid  by  heating  with  thirty  per 
cent,  sulphuric  acid  for  two  hours. 

Nucleic  acid  is  not  precipitated  by  the  reagents  used  for 
the  precipitation  of  proteids,  and  does  not  give  the  color 
reactions  of  proteids.  When  some  of  the  nucleic  acids  are 
boiled  with  dilute  mineral  acids,  a  substance  (carbohydrate) 
is  produced  which  reduces  alkaline  solutions  of  cupric 
oxide. 

The  detection  of  the  nucleic  acids  depends  upon  the  iso- 
lation of  their  chief  constituents — phosphoric  acid  and  xan- 
thin  bases. 

ALLANTOIN. 
C4H8N4O3. 

This  substance  has  been  found  in  the  urine  of  infants 
within  the  first  eight  days  after  birth,  in  new-born  calves 
(Wohler),  and  in  the  urine  of  man  (Ziegler  and  Hermann). 

Allantoin,  when  pure,  crystallizes  in  large  monoclinic 
prisms  with  hexagonal  bases,  often  arranged  in  star-like 
groups  ;  when  impure,  in  warty  and  granular  particles.  It 
has  a  neutral  reaction,  is  difficultly  soluble  in  cold  water 
(160  parts),  more  readily  in  hot  water  (30  parts),  very  sol- 
uble in  alkaline  hydrates,  and,  according  to  Salkowski, 
more  readily  soluble  in  a  solution  of  piperazin  than  in 
water.  It  is  insoluble  in  alcohol  and  ether.  It  combines 
with  acids  and  bases  to  form  salts.  The  compounds  with 
silver  oxide  and  mercuric  oxide  are  particularly  serviceable 
for  the  detection  of  allantoin. 

When  a  freshly  prepared  solution  of  allantoin  in  sodic  or 
potassic  hydrate  is  supersaturated  with  acetic  acid,  it  is 
immediately  precipitated.      It  then  contains  allantoic  acid. 

Allantoin  is  obtainable  from  uric  acid  by  oxidation  with 
potassium  permanganate  : 

aCjH^N^Os  +  2H2O  +  02  =  aC^HgNPs  +  2C0,j. 
Uric  acid.  Allantoin. 

i*'Zeitschr.  f.  physiol.  Cheniie,"  Bd.  xxv,  S.  430. 


ALLANTOIN.  77 

Allantoin  is  decomposed  by  heating  with  hydrochloric 
acid  into  allanturic  acid  and  urea  : 

QIIeN.Oj  +  H,0  =  CgH.Np,  +  CH,N,0. 
Allantoin.  Allanturic  acid.        Urea. 

When  allantoin  is  boiled  with  an  alkali  or  baryta  water, 
it  furnishes  first,  as  in  the  decomposition  with  acids,  allan- 
turic acid  and  urea  ;  but  the  allanturic  acid  is  further  decom- 
posed into  hydantoic  and  parabanic  acids  : 


2C.,H,N,03  = 

^.    CgHgN.Oj    +    CgH^N^Oj. 

Allanturic 
acid. 

Hydantoic          Parabanic 
acid.                     acid. 

and  the  parabanic  acid  is  finally  decomposed  into  oxalic 
acid  and  urea  : 

C3H,N,03  +  2H,0  =  C,H,0;+  CH,N,0. 

Oxalic  Urea, 

acid. 

Allantoin  reduces  Fehling's  solution  on  boiling.  It  is 
not  precipitated  by  lead  acetate  or  phosphotungstic  acid, 
and  does  not  give  the  murexide  reaction. 

Allantoin  is  present  in  normal  urine  in  mere  traces,  ex- 
cept directly  after  birth.  It  has  been  found  to  be  increased 
by  a  meat  diet,  and  by  the  administration  of  tannic  acid. 
Pouchet  found  allantoin  considerably  increased  in  the  urine 
of  a  case  of  diabetes  insipidus  and  in  a  case  of  hysteria 
with  convulsions. 

Detection. — In  order  to  detect  allantoin,  it  must  first 
be  separated  from  the  urine.  The  following  method  of  G. 
Meissner  ^  best  serves  this  purpose  :  Precipitate  the  urine 
with,  baryta  water,  exactly  neutralize  the  filtrate  with  sul- 
phuric acid,  filter  at  once,  and  evaporate  to  beginning 
crystallization.  The  fluid,  while  still  warm,  is  treated  with 
sufficient  alcohol  to  completely  precipitate  (this  precipitate 
should  be  saved).  The  alcoholic  solution  is  then  decanted 
from  the  precipitate  or  filtered  off,  and  completely  precipi- 
tated with  ether.  Both  precipitates,  especially  the  one  ob- 
tained with  the  ether,  contain  the  allantoin  together  with 
other  substances.  The  precipitates  are  then  extracted  with 
a  little  cold  water  or  with  hot  alcohol,  the  allantoin  remain- 
ing undissolved.  Characteristic  crystals  of  allantoin  are 
then  obtained  by  recrystallizing  the  residue  from  hot  water. 

i"Zeitschr.  f.  rat.  Med.,"   [3]  Bd.  xxiv,   104,  u.  Bd.  xxxi,  297. 


78 


ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 


KREATIN  AND  KREATININ. 

CiHgNaOa— CiHjNaO. 

These  two  substances  are  constituents  of  normal  urine. 
They  differ  chemically  in  that  kreatinin  contains  one  mole- 
cule less  of  H2O  than  kreatin,  as  seen  by  the  foregoing 
formulae.  Kreatin,  which  is  constantly  present  in  muscle 
tissue,  is  in  all  probability  the  antecedent  of  kreatinin,  so 
that  two  sources  of  this  substance  must  be  recognized — /.  c, 
the  muscle  tissue  of  the  body  and  the  muscle  tissue  taken 
as  food.  Kreatin  is  more  abundant  in  alkaline  urine  than 
kreatinin,  while  in  a  strongly  acid  urine  the  reverse  is  the 
case.     Since  the  urine  is  generally  acid,  kreatinin  is  the  pre- 


Fig.  9. — Crystals  of  kreatinin-zinc  chloride  (Salkowski). 


dominating  constituent  of  normal  urine,  and  will  be  further 
considered. 

Kreatini)i  crystallizes  without  water  of  crystallization  in 
colorless,  glistening  prisms  of  the  monoclinic  system  ;  some- 
times these  crystals,  when  found  lying  on  their  sides,  appear 
in  the  form  of  whet-stones.  Kreatinin  is  readily  soluble  in 
hot  water  and  quite  soluble  in  cold  water  ;  it  is  very  solu- 
ble in  hot  alcohol,  but  more  difficultly  so  in  cold  alcohol 
and  ether.  It  reduces  alkaline  solutions  of  copper  (Feh- 
ling's  solution)  upon  boiling.  It  forms  salts  with  the  acids, 
and  double  salts  with  some  of  the  salts  of  the  heavy  metals. 
Among    these    may    be    mentioned    kreatinin    chloride    or 


KREATININ.  79 

hydrochlorate,  which  is  easily  soluble  in  water  and  crystal- 
lizes in  the  form  of  transparent  prisms  or  rhombic  plates. 
One  of  the  most  important  of  the  double  salts  is  the  com- 
pound of  kreatinin  with  zinc  chloride  (C^H^N^O)^  .  ZnCl2, 
produced  by  treating  an  aqueous  or  alcoholic  solution  of 
kreatinin  with  zinc  chloride.  If  the  kreatinin  is  pure,  the  com- 
pound crystallizes  in  the  form  of  fine  needles  grouped  together 
in  rosettes  or  sheaves.  (Fig.  9.)  Kreatinin-zinc  chloride 
is  very  slightly  soluble  in  water  and  insoluble  in  alcohol. 

Kreatinin  is  a  constituent  of  normal  human  urine.  Ac- 
cording to  the  determinations  of  Neubauer,  a  healthy  man 
on  a  well-mixed  diet  eliminates  from  0.6  to  1.3  grams  of 
kreatinin  in  twenty-four  hours.  As  indicated,  the  quantity 
of  kreatinin  appears  to  vary  according  to  the  disintegration 
of  muscle  tissue  in  the  body  and  the  amount  of  meat 
ingested  with  the  food. 

Clinically,  it  is  excreted  in  increased  quantity  in  acute  dis- 
eases, such  as  typhoid  fever,  pneumonia,  etc.  It  is  diminished 
in  hunger,  in  convalescence  from  acute  diseases,  in  advanced 
degeneration  of  the  kidneys,  and  in  wasting  diseases. 

Detection  of  Kreatinin. —  i.  JVej/'s  Test. — To  a  {&\n 
cubic  centimeters  of  the  urine  add  a  few  drops  of  a  very 
dilute  solution  of  sodium  nitroprusside,  and  render  alkaline 
with  sodic  hydrate.  If  kreatinin  be  present,  the  mixture 
assumes  a  ruby-red  color,  which  disappears  in  a  few  minutes 
and  is  replaced  by  an  intense  yellow  color,  which,  on 
w^arming  with  glacial  acetic  acid,  gives  rise  to  a  green  color. 
The  presence  of  albumin  and  sugar  does  not  interfere  with 
the  reaction. 

2.  To  a  solution  of  kreatinin  add  a  small  quantity  of  an 
aqueous  solution,  of  picric  acid,  and  then  a  few  drops  of 
dilute  sodic  or  potassic  hydrate.  An  intense  red  color  ap- 
pears. This  red  color  is  apparent  (only  less  intense)  when 
kreatinin  is  present  in  the  proportion  of  i    :   5000  ( Jaffe). 

3.  When  a  solution  of  kreatinin  is  acidulated  with  nitric 
acid  and  treated  with  phosphomolybdic  acid,  a  yellow, 
crystalline  precipitate  is  produced,  which  is  soluble  in  hot 
nitric  acid. 

4.  The  double  compound  of  kreatinin  and  zinc  chloride 
shows,  microscopically,  characteristic  cr^^stals.  (Fig.  9.) 
This  test  is  used  for  the  quantitative  estimation  of  kreatinin.  ^ 

^  See  Neubauer  and  Vogel,  "Analyse  des  Hams,"  Bd.  I,  1898,  S.  396. 


80  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE, 


THE  AROMATIC  SUBSTANCES  IN  URINE. 

The  aromatic  substances  that  occur  in  urine  belong  to 
four  classes  : 

1.  Hippuric  acid,  and  similar  aromatic  compounds  of 
glycocoll. 

2.  Combinations  of  glycuronic  acid  with  aromatic  sub- 
stances.    (See  p.  169.) 

3.  Aromatic  oxyacids. 

4.  Ethereal  sulphates. 

Hippuric  Acid  (CgHgNO,). — Hippuric  acid  is  a  constitu- 
ent of  the  urine  of  man  in  both  health  and  disease.  The 
twenty-four-hour  quantity  of  urine  contains  between  o.i 
and  I  gram     It  is  very  abundant  in  the  urine  of  herbivora, 


Fig.  10. — Hippuric  acid  crystals. 

and  in  man  the  quantity  varies  largely  according  to  the 
amount  of  vegetable  food  ingested.  It  is  absent  from  the 
urine  of  carnivora. 

Hippuric  acid  crystallizes  either  in  the  form  of  fine 
needles  or  four-sided  prisms  and  pillars,  the  ends  of  which 
terminate  in  two  or  four  planes.  (Fig.  10.)  At  times  these 
resemble  the  crystals  of  ammonio-magnesium  phosphate, 
with  which  they  should  not  be  confounded.  Typically,  the 
crystals  of  hippuric  acid  are  in  the  form  of  vertical  rhombic 
prisms. 

Hippuric  acid  is  soluble  in  600  parts  of  water  at  0°  C, 
and  much  more  soluble  in  hot  water  and  alcohol.  Its  solu- 
tions have  a  strongly  acid  reaction.  It  combines  with  bases 
to  form  salts.  Its  compounds  with  the  alkalies  and  alkaline 
earths  are  soluble  in  water  and  alcohol,  but  the  silver,  cop- 
per, and  lead  salts  are  difficultly  soluble  in  water.  Strong 
acids   precipitate   the    hippuric    acid    from   its   salts,  and  it 


HIPPURIC  ACID.  81 

reappears  in  crystalline  form.  When  hippuric  acid  is  boiled 
with  an  alkaline  hydrate  or  with  mineral  acids,  it  takes  up 
a  molecule  of  water  and  is  decomposed  into  benzoic  acid 
and  glycocoll  : 

CgHj  .  CO  —  HN  .  CH,  .  COOH  +  Hfi  = 
Hippuric  acid. 

CgHs  .  COOH  +  HjN  .  CH2  .  COOH. 
Benzoic  acid.  Glycocoll. 

This  same  decomposition  takes  place  during  the  alkaline 
fermentation  of  the  urine,  especially  of  urine  containing 
albumin,  the  hippuric  acid  being  acted  upon  by  the  micro- 
coccus ureae.  No  hippuric  acid,  therefore,  is  found  in 
decomposing  urine,  benzoic  acid  taking  its  place.  Hippuric 
acid  reduces  alkaline  solutions  of  cupric  oxide  (Fehling's 
solution)  on  boiling. 

The  experiments  of  Meissner  and  Shepard,  and  of 
Schmiedeberg  and  Bunge  show  that  hippuric  acid  is  prob- 
ably formed  by  the  union  of  benzoic  acid  and  glycocoll, 
and  that  this  union  takes  place  in  the  kidneys,  as  they 
failed  to  find  that  the  synthesis  occurred  after  the  removal 
of  the   kidneys. 

As  previously  indicated,  the  amount  of  hippuric  acid  in 
the  urine  of  man  is  dependent  chiefly  upon  the  character 
and  quantity  of  food  ingested,  being  increased  by  a  vege- 
table diet,  especially  by  certain  fruits,  as  prunes,  mulberries, 
cranberries,  blueberries,  or  by  any  substance  containing  the 
benzoic  acid  radicle.  It  is  increased  by  the  administration 
of  benzoic  acid,  cinnamic  acid,  oil  of  bitter  almonds,  salicylic 
acid,  toluol,  etc.  ;  also  in  acute  febrile  diseases,  hepatic  dis- 
eases, diabetes  mellitus,  and  cholera.  It  is  diminished  by 
an  exclusive  meat  diet,  although  generally  it  does  not  dis- 
appear entirely  from  the  urine  upon  such  a  diet.  It  is  an 
interesting  fact  that,  in  accordance  with  Bunge's  experi- 
ments on  dogs,  the  elimination  of  hippuric  acid  appears  to 
be  wholly  suspended  in  ca.ses  of  acute  and  chronic  paren- 
chymatous nephritis,  following  the  ingestion  of  benzoic  acid, 
which  reappears  in  the  urine  unchanged. 

Detection.— When  urine  containing  hippuric  acid  or  one 
of  its  salts  is  evaporated  to  dryness  with  concentrated  nitric 
acid,  and  the  residue  is  heated  in  a  test-tube,  the  odor  of 
bitter  almonds  is  noticed,  due  to  the  formation  of  nitro- 
benzol  (benzoic  acid  gives  the  same  result). 
6 


82  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

Hippuric  acid  may  be  separated  from  urine  containing  an 
excess  of  it  by  evaporating  the  urine  to  one-fourth  of  its 
volume  and  acidulating  with  hydrochloric  acid.  In  a  few 
hours  characteristic  crystals  of  hippuric  acid  will  be  found 
in  the  deposit,  when  examined  microscopically. 

Quantitative  Kstimation.  —  Ma/iod. — From  500  to 
1000  c.c.  of  fresh  urine  are  evaporated  to  a  syrupy  con- 
sistence on  a  water-bath,  care  being  taken  to  keep  the  urine 
neutral  by  the  addition  of  sodium  carbonate.  The  residue  is 
extracted  with  cold  alcohol  (ninety  to  ninety-five  per  cent.), 
taking  a  quantity  about  half  as  great  as  that  of  urine  em- 
ployed, and  setting  aside  the  mixture  for  twenty-four  hours. 
The  alcohoHc  filtrate,  which  contains  the  salts  of  hippuric 
acid,  is  then  freed  from  alcohol  by  distillation.  The  remain- 
ing solution  is  strongly  acidulated  with  acetic  acid,  in  order 
to  liberate  the  lactic  acid,  and  extracted  with  at  least  five 
times  its  own  volume  of  alcoholic  ether  (one  part  of  alcohol 
to  nine  parts  of  ether).  From  the  combined  extracts  the 
ether  is  distilled  off  and  the  remaining  solution  evaporated 
on  a  water-bath.  The  resinous  residue  is  boiled  with 
water,  set  aside  to  cool,  and  filtered  through  a  well-moist- 
ened filter.  The  hippuric  acid,  which  is  easily  soluble  in 
boiling  water,  is  thus  separated  from  constituents  that  are 
soluble  in  alcohol  and  ether.  The  filtrate  is  rendered  alka- 
line with  a  little  milk  of  lime,  any  excess  of  calcium  hydrate 
being  removed  by  passing  carbon  dioxide  through  the  mix- 
ture. This  mixture  is  then  brought  to  the  boiling-point  and 
filtered.  Any  impurities  present  are  removed  by  shaking 
with  ether.  The  calcium  salts  remaining  in  solution  are 
decomposed  by  means  of  an  acid,  and  the  solution  is  again 
extracted  with  ether.  The  remaining  solution  is  evaporated 
to  a  few  cubic  centimeters,  when  the  hippuric  acid  will  sepa- 
rate on  standing.  The  crystals  are  dried  on  plates  of  plaster- 
of- Paris  ;  they  are  then  shaken  with  benzol  or  petroleum 
ether  to  remove  any  benzoic  acid,  and  finally  weighed. 
These  crystals  may  be  shown  to  be  hippuric  acid  by  their 
microscopic  appearance,  their  solubility  in  alcohol,  and 
their  behavior  when  evaporated  with  concentrated  nitric 
acid,  as  previously  indicated. 

Aromatic  Oxyacids. — Two  of  these,  hydroparacumaric 
acid  and  paraoxyphenyl-acetic  acid,  are  found  in  the  urine 
in  small  quantities  in  combination  with  potassium.  They 
apparently  are  derived  from   the   decomposition   that  takes 


ETHEREAL  SULPHATES.  83 

place  in  proteids  in   the  intestine  ;  tryosin    is   probably  an 
intermediate  product  (Baumann)  ; 

CgH„N03  +  H,  =  C^HioOj  +  NH3. 

Tyrosin.  Hydropara- 

cumaric  acid. 

C,H,„0,  =  C,Hi„0  +  CO,. 

Hydiopara-  Paraethyl 

cumaric  acid.  phenol. 

C«H,„0  4-  O3  =  CgHgOs  +  H,0. 
Paraethyl  Paraoxy- 

pheiiol.  phenyl-acetic 

acid. 

Ethereal  Sulphates. — A  few  of  the  products  of  decom- 
position are  of  especial  interest  because  of  their  behavior 
within  the  body,  and  because  after  their  absorption  they 
appear  in  the  urine  in  the  form  of  ethereal  or  conjugate  sul- 
phates of  sodium  and  potassium.  A  few,  such  as  the  oxy- 
acids,  pass  unchanged  into  the  urine ;  others,  such  as 
phenols,  are  changed  into  ethereal  sulphates  by  synthesis, 
and  are  eliminated  by  the  urine.  Still  others,  such  as  indol 
and  skatol,  are  converted  into  ethereal  sulphates  only  after 
oxidation.  The  quantities  of  these  bodies  in  the  urine  vary 
largely  with  the  extent  of  the  putrefaction  that  is  constantly 
taking  place  in  the  intestine. 

The  earliest  information  bearing  upon  this  subject  was 
furnished  in  185  i  by  Stadeler,  who  found  that  on  distilling 
the  urine  of  oxen  and  of  men  with  dilute  sulphuric  acid,  he 
obtained  in  the  distillate  small  amounts  of  phenol.  It  was 
not,  however,  until  1875  that  Baumann  discovered  that 
phenol  existed  in  an  ethereal  combination  with  sulphuric 
acid.  He  also  determined  the  presence  of  other  ethereal 
sulphates,  all  of  which  were  found  to  be  compounds  of  the 
radicle  HSO.,. 

The  ethereal  sulphates  appear  to  have  one  or  both  of  two 
origins:  (i)  From  the  aromatic  substances  in  the  food; 
hence  their  greater  abundance  in  the  urine  of  herbivora. 
(2)  From  the  intestine  as  a  result  of  putrefaction.  They 
are  absorbed  from  the  intestine,  pass  into  the  blood,  and 
are  eliminated  in  the  urine  in  combination  with  potassium 
and  sodium  as  ethereal  sulphates. 

A  large  number  of  determinations  have  been  made  rela- 
tive to  the  proportion  of  the  ethereal  sulphates  to  the 
ordinary  (alkaline)  sulphates  in  the  urine  of  man,  and  the 
normal  proportion  may  be  stated  as  about  i  :  10. 


84  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

In  disease,  whenever  the  putrefaction  in  the  intestine  or 
in  other  parts  of  the  body  is  increased,  the  proportion  of 
ethereal  sulphates  rises.  The  investigations  of  G.  Hoppe- 
Seyler  are  noteworthy,  his  results  being  summarized  as  fol- 
lows : 

1.  Deficient  absorption  of  the  normal  products  of  digestion, 
such  as  occurs  in  peritonitis  and  tubercular  disease  of  the  intes- 
tine, leads  to  an  increase  of  the  ethereal  sulphates  in  the  urine, 
because  the  products  of  digestion  undergo  putrefactive  changes, 
and  the  putrefactive  products  are  absorbed. 

2.  Diseases  of  the  stomach,  in  which  the  food  lies  in  the 
stomach  a  long  time  and  undergoes  fermentative  changes, 
always  lead  to  an  increase  of  the  ethereal  sulphates  in  the  urine. 

3.  Simple  constipation  and  typhoid  fever  do  not  produce  this 
result. 

4.  Putrefactive  processes  outside  the  alimentary  canal,  putrid 
cystitis,  putrid  abscesses,  putrid  peritonitis,  etc.,  have  the  same 
result  as  putrefactive  processes  within  the  intestine.  The  amount 
of  the  ethereal  sulphates  is,  moreover,  in  all  cases  proportional 
to  the  degree  of  the  putrefaction,  and  is  increased  by  the  reten- 
tion and  diminished  by  the  discharge  of  putrid  matter. 

It  has  been  conclusively  shown  b)-  these  and  other  obser- 
vations that  the  best  criterion  of  the  occurrence  and  amount 
of  putrefaction  in  the  body  is  the  relation  of  the  ethereal 
sulphates  to  the  total  sulphates. 

Indoxyl-potassium  Sulphate  (C^H^.NO  .  SO^ .  OK),  In- 
doxyl — Indican  (/) — This  substance  is  formed  from  indol, 
— CgH^N, — which  is  a  product  of  the  putrefaction  of 
albuminous  substances  in  the  intestine.  The  indol  is  then 
absorbed  from  the  intestine  and  enters  the  blood,  where 
it  becomes  oxidized  to  indoxyl, — C^H^jNO, — which  imme- 
diately combines  with  potassium  (and  to  a  slight  extent 
with  sodium)  sulphate  to  form  indoxyl-potassium  sulphate, 
in  which  form  it  is  eliminated  in  the  urine. 

By  the  oxidation  of  indoxyl-potassium  sulphate  indigo- 
blue  is  formed  : 

zCgHgNKSO^  -(-  O,  =  aC.HjNO  +  2HK  .  SO,. 

Indoxyl-potassium  Indigo-blue.       Potassium  hy- 

sulphale.  drate  sulphate. 

Indigo-red,  which  has  the  same  elementary  composition 
as  indigo-blue,  is  also  one  of  the  products  of  the  oxidation 
of  indoxyl  sulphate. 

Indoxyl   is   a  constituent  of  normal   human    urine,  as  a 


INDOXYL-POTASSIUM  SULPHATE.  85 

result  of  the  natural  intestinal  putrefaction.  It  is  absent 
from  tiie  urine  of  the  new-born. 

Under  ordinary  conditions  indoxyl  does  not  contribute  to 
the  color  of  freshly  passed  urine.  It  may,  however,  become 
partially  oxidized  in  the  body,  especially  in  disease,  or  oxida- 
tion may  take  place  outside  of  the  body  during  the  am- 
moniacal  decomposition  of  the  urine,  when  it  probably 
furnishes  some  color  to  the  urine.  In  rare  instances  the 
indoxyl  sulphate  is  completely  oxidized  within  the  body, 
and  a  blue  color  is  imparted  to  the  urine,  due  to  the  deposit 
of  indigo-blue.  Furthermore,  indigo  calculi  have  been 
found  in  the  urinary  tract  following  the  long-continued 
separation  of  indigo  from  the  urine,  but  such  instances  are 
of  very  rare  occurrence. 

The  quantity  of  indoxyl  separated  from  the  urine  as  in- 
digo-blue has  been  found  to  be  between  0.005  ^''"'^1  0.025 
gram  in  the  twenty-four-hour  secretion  of  a  healthy  indi- 
vidual on  a  mixed  diet  (Neubauer  and  Vogel).  The  largest 
quantities  excreted  in  health  are  observed  after  a  liberal  in- 
gestion of  a  meat  diet,  particularly  the  so-called  red  meats, 
while  the  smallest  quantities  have  been  found  during  the 
ingestion  of  a  milk  diet. 

Clinical  Significance. — The  clinical  importance  of  in- 
doxyl rests  chiefly  upon  its  increased  elimination,  its  dimi- 
nution having  little  or  no  importance.  Indoxyl  is  increased : 
(i)  In  all  cases  of  increased  intestinal  putrefaction,  espe- 
cially that  taking  place  in  the  small  intestine.  Thus,  in 
diarrhea  it  is  increased,  whereas  in  dysentery  (disease  of 
the  large  intestine)  no  such  increase  takes  place.  It  is  in- 
creased in  typhoid  fever  and  in  cholera,  also  in  some  forms 
of  Bright's  disease,  notably  chronic  diffuse,  chronic  inter- 
stitial, and  subacute  glomerular  nephritis.  Simon  has  ob- 
served an  increase  in  cases  in  which  the  gastric  juices 
contained  an  abnormally  small  amount  of  free  hydrochloric 
acid  or  in  which  it  was  absent  entirely,  notably  carcinoma  of 
the  stomach,  and  he  believes  that  it  is  possible  to  form  a 
fairly  accurate  idea  of  the  amount  of  free  hydrochloric  acid  in 
the  stomach  by  examining  the  urine  for  indoxyl.  There  are 
exceptions  to  this,  however,  to  explain  which  he  grants  is  im- 
possible at  the  present  time.  Indoxyl  is  also  increased  in 
acute,  subacute,  and  chronic  gastritis  of  whatever  origin  ;  in 
acute  peritonitis  (marked  increase),  cancer  of  the  mesentery, 
appendicitis,  diseases   of  the  liver  and  pancreas,  especially 


86  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

those  accompanied  by  an  acute  peritonitis  ;  in  Addison's 
disease,  lead  colic,  and,  in  short,  in  any  disease  of  the  ab- 
dominal viscera  accompanied  by  an  increase  in  the  intestinal 
putrefaction.  It  is  also  increased  in  acute  diseases  elsewhere 
in  the  body,  as  in  pneumonia,  pleurisy,  meningitis,  acute 
articular  rheumatism,  etc. 

(2)  The  indoxyl  is  increased  by  any  condition  that  pre- 
vents the  passage  of  fecal  matter  through  the  small  intes- 
tine, as  in  intussusception,  twists,  new  growths,  and  the  like. 
In  diseases  of  the  large  intestine  an  increase  of  indoxyl  is 
never  seen  ;  thus,  the  tests  for  indoxyl  in  the  urine  are  of 
decided  value  in  the  differential  diagnosis.  In  simple,  un- 
complicated constipation  the  indoxyl  is  not  increased. 

(3)  An  increase  in  the  indoxyl  is  also  seen  when  albu- 
minous putrefaction  takes  place  in  other  parts  of  the  body, 
as  in  cases  of  empyema,  putrid  bronchitis,  gangrene  of  the 
lungs,  advanced  phthisis,  etc. 

There  can  be  no  doubt  of  the  clinical  significance  of  the 
test  for  indoxyl  in  the  urine,  for  points  of  decided  importance, 
not  only  in  diagnosis,  but  also  in  prognosis  and  treatment, 
can  thus  be  gained. 

Detection. — (i)  The  following  color  reaction  depends 
upon  the  decomposition  and  oxidation  of  the  indoxyl-sul- 
phate  of  potassium  by  means  of  hydrochloric  acid,  the 
oxidation  being  accelerated  by  the  use  of  nitric  acid.  The 
color  that  results  usually  consists  of  a  mixture  of  indigo- 
blue  and  indigo-red  (amethyst). 

Take  15  c.c.  of  strong  hydrochloric  acid  (C.  P.)  in  a  wine- 
glass, add  one  or  two  drops  of  strong  nitric  acid  (C.  P.), 
stir,  then  add  thirty  drops  of  the  urine  to  be  tested,  and 
stir  immediately.  An  amethyst  color  soon  makes  its  ap- 
pearance, reaching  its  greatest  intensity  in  from  five  to 
twenty  minutes.  The  amount  of  color  obtained  at  the  point 
of  greatest  intensity  furnishes  some  data  as  to  the  amount 
of  indoxyl  present.  If  normal,  a  distinct  but  not  intense 
amethyst  color  appears  ;  if  increased,  the  color  is  decided 
and  often  very  deep  ;  and  if  diminished,  there  will  be  but 
very  little  color,  and  rarely  an  entire  absence  of  color. 

The  reaction  can  also  be  obtained  by  using  hydrochloric 
acid  alone,  but  has  the  disadvantage  of  requiring  a  longer 
time  for  the  greatest  color  to  appear.  It  is,  therefore,  ad- 
visable to  add  one  or  two  drops  of  nitric  acid  in  order  to 
hasten  oxidation,  care  being  taken  not  to  add  more,  or  the 


SKATOXYL-POTASSIUM  SULPHATE.  87 

oxidation  will  be  so  rapid  that  the  amethyst  color  can  not 
be  seen,  only  a  yellow  color  resulting.  ^ 

The  thirty  drops  of  urine  added  should  always  be  uni- 
form in  size,  and  such  as  are  obtained  when  the  urine  is 
dropped  from  the  lip  of  a  urinometer-glass.  (Fig.  2.)  It 
is,  therefore,  advisable  to  have  a  pipette  for  the  perform- 
ance of  the  test,  made  by  dropping  thirty  drops  of  urine 
into  a  wine-glass,  then  drawing  it  up  into  the  pipette,  and 
indicating  the  level  of  tlie  urine  by  means  of  a  scratch  on 
the  glass. 

In  urine  containing  potassium  iodide  the  test  for  indoxyl 
can  not  be  satisfactorily  applied,  particularly  if  hydrochloric 
acid  containing  free  hydrochloric-acid  gas  be  used,  or  if 
nitric  acid  be  added  to  the  hydrochloric  acid.  This  is 
because  of  the  oxidizing  action  of  the  iodine  that  is  set 
free.  Under  such  circumstances  a  yellow  color  imme- 
diately results  ;  in  other  words,  the  oxidation  is  so  rapid 
that  the  amethyst  color  can  not  be  seen. 

(2)  Take  about  10  c.c.  of  the  urine  in  a  test-tube,  add  an 
equal  volume  of  hydrochloric  acid  and  a  few  drops  of  a 
freshly  prepared  saturated  solution  of  sodium  hypochlorite, 
calcium  hypochlorite,  or  common  saltpeter,  and  then  i  or  2 
c.c.  of  chloroform.  The  mixture  is  thoroughly  agitated  and 
set  aside.  The  indigo  that  has  been  set  free  is  taken  up 
by  the  chloroform,  coloring  this  to  a  greater  or  less  extent, 
the  degree  of  increase  as  compared  with  the  normal  being 
determined  by  the  intensity  of  color. 

Albumin  does  not  interfere  with  these  two  tests.  Bile 
pigment,  which  interferes  with  the  reaction,  may  be  removed 
by  the  addition  of  a  solution  of  basic  acetate  of  lead,  care- 
fully avoiding  an  excess.  Urines  presenting  a  very  dark 
color  may  be  freed  from  the  greater  part  of  their  coloring- 
matter  in  the  same  manner.  If  potassium  iodide  be  present, 
the  chloroform  will  be  colored  more  or  less  of  a  carmine, 
owing  to  the  liberation  of  free  iodine. 

Skatoxyl-potassium  Sulphate  (C„H^NO  .  SO^K  ).— 
This  substance  is  formed  from  skatol,  which,  like  indol,  is  a 
product  of  the  putrefaction  of  proteids  in  the  intestine. 
Some  of  it  is  absorbed  by  the  blood,  where  it  combines 
w^ith  potassium  sulphate,  in  which  form  it  is   eliminated  in 

1  If  hydrochloric  acid  containing  much  free  hydrochloric-acid  gas  be  used 
for  the  test,  nitric  acid  should  not  be  added,  since  the  oxidation  is  effected  by 
the  free  gas  present. 


88  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

the  urine  as  a  colorless  compound,  and  when  it  is  oxidized, 
it  yields  a  red  color. 

Skatoxyl-potassium  sulphate  is  a  constituent  of  normal 
urine,  but  is  usually  present  in  smaller  quantities  than  the 
indoxyl  sulphate. 

Clinically,  this  substance  is  of  little  interest  except  in 
connection  with  indoxyl,  and  since  both  the  skatoxyl  and 
indoxyl  sulphates  are,  clinically,  considered  as  one,  it  is  not 
necessary  here  to  enter  into  the  consideration  of  its  proper- 
ties or  modes  of  detection  further  than  to  state  that  the 
indigo-red  oxidation  products  obtained  in  the  tests  for 
indoxyl  are  probably  partly  due  to  the  presence  of  skatoxyl- 
potassium  sulphate. 

Phenol-potassium  Sulphate  (C,.H.O  SO.j .  K). — Phenol, 
C^^HyO,  is  one  of  the  products  of  intestinal  putrefaction. 
The  production  of  phenol  probabh'  takes  place  lower  down 
in  the  small  intestine  than  indol,  but  higher  up  in  the  intes- 
tine than  skatol.  It  is  absorbed  from  the  intestine,  and, 
entering  the  blood,  combines  with  potassium  sulphate  to 
form  the  ethereal  or  conjugate  sulphate,  phenol-potassium 
sulphate.  According  to  Baumann,  some  of  the  sulphate 
comes  from  tyrosine,  which  passes  through  the  stages  of 
parakresol  and  paraoxybenzoic  acid  before  conversion  into 
the  phenol  salt.  This  substance  is  the  form  in  which  all 
of  the  phenol  or  carbolic  acid  of  the  body  exists.  It  is  a 
constituent  of  normal  urine,  and  is  present  in  amounts  vary- 
ing between  0.017  and  0.5  gram — an  average  of  about  0.03 
gram — for  twenty-four  hours.  Phenol  sulphuric  acid  is 
abundant  in  the  urine  of  herbivora. 

A  urine  rich  in  indoxyl  usually  contains  an  excess  of 
phenol,  but  one  rich  in  phenol  does  not  always  contain  an 
excess  of  indoxyl.  In  those  cases  in  which  an  increased 
elimination  of  ethereal  sulphates  is  due  to  albuminous  putre- 
faction in  other  parts  of  the  body  than  the  intestine,  as  in 
empyema,  pulmonary  gangrene,  putrid  bronchitis,  etc.,  an 
increased  elimination  of  phenol  alone  may  be  noted,  the 
amount  of  indoxyl  being  about  normal. 

Clinical  Significance. — The  use  internally  or  externally 
of  large  amounts  of  carbolic  acid,  lysol,  salol,  and  other 
phenol  compounds  results  in  an  increase  in  the  amount  of 
phenol  sulphate  and  a  corresponding  diminution  in  the  ordi- 
nary sulphates,  the  latter  being  taken  up  by  the  excess  of 
phenol  in  the  blood.     Two  substances,  pyrocatechin  and 


PHENOL-POTASSIUM  SULPHATE.  89 

hydrochinon,  are  formed  as  a  result  of  the  splitting  up  of 
carbolic  acid.  Urines  containing  these  substances,  although 
usually  normal  in  color  when  voided,  become  smoky,  dark 
brown,  or  black  on  standing  exposed  to  the  air.  This  dark 
color  is  often  more  pronounced  after  alkaline  decomposition 
begins,  and  is,  in  all  probability,  due  to  the  oxidation  pro- 
ducts of  hydrochinon. 

The  phenol  sulphate  is  increased  in  those  conditions  that 
cause  increased  putrefaction  in  the  lower  part  of  the  small 
intestine  and  upper  portion  of  the  large  intestine.  In  other 
words,  most  of  the  conditions  that  cause  an  increase  in 
the  indoxyl  sulphate  also  cause  an  increase  in  the  phenol 
sulphate.  Its  increase  is  especially  marked  in  peritonitis, 
pyemia,  and  in  phosphorus-poisoning. 

Detection. — Distil  the  urine  with  sufficient  sulphuric 
acid  to  make  a  five  per  cent,  mixture,  (i)  To  a  portion  of 
the  distillate  add  bromine  water,  which  gives  a  yellow  pre- 
cipitate of  tribromphenol.  (2)  To  another  portion  add  Mil- 
Ion's  reagent,  and  heat.  A  beautiful  red  color  results. 
(3)  Saturate  still  another  portion  of  the  distillate  with  sodic 
carbonate  in  the  cold,  and  shake  with  ether  in  order  to 
remove  salicylic  acid  and  other  substances  that  give  a  ferric 
chloride  reaction.  Evaporate  the  ether,  and  to  an  aqueous 
solution  of  the  residue  add  ferric  chloride,  which  gives  a 
deep  violet  color. 

Determination. — The  following  procedure  may  be  ap- 
plied for  the  determination  of  phenol  in  urine  :  Take  500  to 
lOOO  c.c.  of  the  urine,  treat  with  sufficient  sulphuric  acid  to 
represent  five  per  cent,  of  the  mixture,  and  distil  as  long  as 
a  specimen  of  the  distillate  is  rendered  cloudy  by  bromine 
water  (i  :  30),  the  specimens  used  for  this  purpose  being 
carefully  preserved.  The  total  quantity  of  the  filtered  dis- 
tillate, together  with  the  specimens  that  have  been  set 
aside,  is  now  treated  with  bromine  water,  shaking  the  mix- 
ture after  each  addition  of  the  reagent  until  a  permanent 
yellow  color  results.  After  two  or  three  days  the  precipi- 
tate of  tribromphenol  that  forms  is  collected  on  a  filter  that 
has  been  previously  dried  and  weighed,  washed  with  water 
containing  a  trace  of  bromine,  and  then  dried  over  sulphuric 
acid  and  weighed.  One  hundred  parts  of  tribromphenol 
correspond  to  28.4  parts  of  phenol. 

The  urine  contains  small  quantities  of  two  other  ethereal 
sulphates  :  i.  c,  kresol-potassiuin  sulphate  and  katccJiol-potas- 


90  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

stwn  sulphate.  These  have  practically  the  same  significance 
as  those  already  considered,  so  that  only  mere  mention  here 
is  necessary.  For  a  detailed  consideration  of  these  sub- 
stances see  Neubauer  and  Vogel,  "  Analyse  des  Hams," 
Bd.  I,  1898,  S.  156  and  158. 


URINARY  COLORING-MATTERS. 

Urobilin  (CgjH^gN^O^). — Normal  urobilin  was  first  isolated 
from  the  urine  by  Jaffe  (1868).  Although  this  substance 
has  for  a  long  time  been  considered  the  chief  coloring- 
matter  of  the  urine,  it  probably  contributes  very  little  to  the 
color  of  the  freshly  passed  urine  of  a  healthy  individual. 
Normal  urobilin  is  present  in  the  urine  chiefly  as  a  chro- 
mogen, — urobilinogen, — and  it  is  not  until  this  chromogen 
is  decomposed  that  its  color  is  set  free.  In  many  pathologic 
conditions,  on  the  other  hand,  there  appears  to  be  a  larger 
amount  of  free  urobilin  than  normally,  and  to  this  MacMunn 
has  given  the  name  "pathological  urobilin."  This  can  be 
artificially  prepared  from  normal  urobilin  by  the  action  of 
reducing  agents. 

Normal  urobilin  is  amorphous  and  not  deliquescent.  Its 
color  varies  according  to  the  method  of  isolation  :  that  pre- 
cipitated by  means  of  ammonium  sulphate  is  brown  ;  that 
precipitated  upon  the  addition  of  an  acid  to  its  alkaline 
solution  is  red  ;  and  that  obtained  by  the  evaporation  of  its 
alcoholic  solution  is  reddish-brown.  It  is  readily  soluble  in 
alcohol  and  chloroform,  also  in  ether,  acids,  and  amnionic 
hydrate.  It  is  very  sparingly  soluble  in  water.  Neutral 
salts  increase  its  solubility  in  water,  but  by  saturating  its 
solution  with  some  of  these  salts  it  is  more  or  less  com- 
pletely precipitated.  It  combines  with  alkalies  to  form 
salts,  and  is  precipitated  from  solutions  of  these  salts  upon 
the  addition  of  acids. 

When  an  acid  solution  of  normal  urobilin  is  examined 
with  the  spectroscope,  it  shows  a  broad  absorption  band  to 
the  right  of  E,  the  left  border  of  which  reaches  nearly  to 
b,  while  the  right  border  incloses  F.  In  alkaline  solu- 
tion it  shows  a  less  broad  absorption  band  between  E  and  F, 
inclosing/;.     (Fig.  11.) 

The  origin  of  urobilin  has  been  the  subject  of  much  dis- 
cussion. Two  theories  have  been  advanced:  (i)  That 
urobilin  is  formed  from  the  bilirubin  which  enters  the  in- 


UROBILIN. 


91 


testine  with  the  bile,  is  there  acted  upon  by  the  nascent 
hydrogen  resulting  from  fermentation,  a  reduction  product 
being  formed  which  is  absorbed  and  eliminated  by  the  kid- 
neys ;  (2)  that  urobilin  is  formed  rather  as  the  result  of  oxi- 
dation processes  by  means  of  the  nascent  oxygen  in  the 
intestine,  or  elsewhere  in  the  body,  than  by  a  process  of 
reduction.  This  theory  was  originally  advanced  by  Mac- 
Munn,  who  based  his  view  chiefly  on  the  fact  that  by  the 
action  of  hydrogen  peroxide  on  acid  hematin  he  was  able 
to  prepare  an  artificial  product  which  showed  the  same 
spectroscopic  appearances  as  normal  urobilin.  Hoppe- 
Seyler  had  previously  prepared  an  artificial  urobilin  from 
hemoglobin,  and  also  from   hematin,  by  the  action   of  tin 


Fig.  II. — I,  Acid  urobilin  ;  2,  alkaline  urobilin  (after  Neubauer  and  \'ogel). 


and  hydrochloric  acid.  Whether  stercobilin  and  urobilin 
are'to  be  looked  upon  as  products  of  reduction  or  oxidation 
must,  therefore,  still  be  regarded  as  unsettled.  The  most 
important  point  to  notice,  however,  is  that  urobilin  may 
originate  either  from  bile  pigment  or  from  blood  pigment. 
It  has  been  conclusively  proved  that  the  bile  pigment  is 
formed  from  hemoglobin  ;  and  that  in  nearly  all  diseases  of 
the  liver  accompanied  by  jaundice,  urobilin  is  largely  in- 
creased in  the  urine.  Furthermore,  that  those  conditions 
which  are  attended  with  a  destruction  of  the  blood-corpus- 
cles are  accompanied  by  an  increased  amount  of  urobilin  in 
the  urine.  It  is,  therefore,  safe  to  infer  that  the  amount  of 
urobilin  in  the  urine  is  a  measure  of  the  destruction  of  the 
hemoglobin,  or  blood  pigment. 


92  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

The  average  quantity  of  urobilin  in  the  twenty-four-hour 
urine,  under  normal  conditions,  is  123  milligrams;  in  dis- 
ease the  quantity  may  reach  800  milligrams.  The  excre- 
tion of  urobilin  is  greater  in  the  tropical  than  in  the  temper- 
ate climates  (Lawson). 

Clinical  Significance. — Urobilin  is  increased  in  acute 
infectious  diseases,  such  as  scarlet  fever,  pneumonia,  erysip- 
elas, malaria,  typhoid  fever  (moderately  increased)  ;  also  in 
acute  sepsis,  lymphangitis,  acute  articular  rheumatism, appen- 
dicitis, atrophic  cirrhosis  and  carcinoma  of  the  liver,  catarrhal 
icterus,  lead  colic,  and  pernicious  anemia.  It  is  also  in- 
creased in  cases  of  poisoning  by  potassium  chlorate,  anti- 
pyrin,  antifebrin,  and  pyridin.  On  the  other  hand,  it  is 
nearly  absent  from  the  urine  in  phosphorus-poisoning. 

Detection.! — Urobilin  is  best  detected  by  means  of  the 
spectroscope:  (i)  Take  from  10  to  20  c.c.  of  the  urine, 
acidulate  with  a  few  drops  of  hydrochloric  acid,  and  shake 
with  from  6  to  10  c.c.  of  amyl  alcohol.  On  spectroscopic 
examination  the  clear  amyl-alcohol  solution  of  urobilin 
shows  a  characteristic  absorption  band  of  acid  urobiHn. 
(Fig.  II.)  (2)  If  to  a  small  portion  of  this  amyl-alcohol 
solution  be  added  a  few  drops  of  a  clear  solution  of  i  gram 
of  zinc  chloride  in  100  c.c.  of  alcohol  that  has  been  ren- 
dered strongly  alkaline  with  ammonia,  a  beautiful  green 
fluorescence  appears.  This  solution  shows  the  spectrum  of 
alkaline  urobilin.      (Fig.  1 1 .) 

For  the  isolation  of  urobilin  the  reader  is  referred  to  more 
extensive  works  on  urinary  analysis. 

Urochrome. — This  substance  is  the  chief  coloring-matter 
of  normal  and  pathologic  urine,  and  imparts  a  yellow,  orange, 
and  even  a  brownish  color  to  the  urine.  According  to 
Garrod,^  a  urate  sediment  always  contains  some  urochrome, 

1  An  old  test,  and  one  frequently  applied  for  the  detection  and  approximate 
estimation  of  urobilin,  is  the  so-called  urophaein  test  (^Heller)  :  Take  about 
seven  cubic  centimeters  of  concentrated  sulphuric  acid  in  a  wine-glass,  and  add 
twice  the  quantity  of  urine,  which  is  poured  into  the  acid  from  a  height  of 
about  four  inches.  A  garnet-red  color  appears  which,  if  normal  in  amount, 
is  so  intense  that  only  a  little  light  can  be  seen  through  the  mixture.  If 
increased,  the  mixture  is  opaque,  and  if  diniinished,  it  is  transparent.  This 
test  is  most  unsatisfactory,  as  normal  coloring-matters  other  than  urobilin  are 
set  free  by  the  acid.  Tliis  test  is  also  modified  by  the  presence  of  abnormal 
constituents,  .such  as  bile,  sugar,  etc.  The  test,  therefore,  is  of  very  little,  if 
of  any,  importance  for  the  detection  or  approximate  determination  of  urobilin 
in  urine. 

">■  "  Journ.  of  Physiol.,"  xvii,  441,  1^95. 


UROCIIROME.  93 

either  alone  or  with  urocrythrin  and  other  coloring-matters. 
The  name  urochromc  was  first  applied  in  1 864  by  Thudichum, 
who  then  considered  it  the  chief  coloring-matter  of  the 
urine.  Urochrome  is  thought  by  some  to  consist  of  impure 
urobilin.  It  probably  does  contain  some  urobilin,  but  that 
it  is  an  independent  substance  has  been  satisfactorily  demon- 
strated by  Thudichum,  Garrod,  and  others. 

Urochrome  contains  nitrogen,  but  is  free  from  iron.  Its 
solutions  have  an  amphoteric  reaction.  In  a  dry  state  it  is 
amorphous,  and  has  a  brown  color.  It  is  odorless  in  the 
cold,  but  w  hen  heated  over  the  water-bath  it  has  a  faint 
odor  of  urine.  It  is  very  readily  soluble  in  water  and  alco- 
hol ;  only  sparingly  soluble  in  acetic  ether,  amyl  alcohol, 
and  acetone  ;  and  is  insoluble  in  ether,  chloroform,  and 
benzol.  Its  solution,  on  the  addition  of  an  acid,  shows 
only  a  diffused  absorption  of  the  spectrum  at  the  violet  end. 
According  to  Thudichum,  the  acid  alcoholic  solution  shows 
a  faint,  narrow  absorption  band  between  F  and  G,  its  left 
edge  bordering  on  F.  The  neutral  and  alkaline  solutions 
do  not  show  absorption  bands.  It  is  precipitated  by  phos- 
photungstic  and  phosphomolybdic  acids,  acetate  of  lead, 
silver  nitrate,  mercuric  acetate,  and  also  by  saturating  its 
solution  with  ammonium  sulphate. 

When  uric  acid  is  precipitated  from  a  solution  that  has 
been  treated  with  urochrome,  the  crystals  are  of  a  yellow  or 
even  brown  color,  and  of  the  whetstone  shape,  the  same  as 
when  they  crystallize  from  the  urine  spontaneously.  When 
uric  acid  is  precipitated  by  an  acid  from  a  solution  con- 
taining urochrome,  the  crystals  are  colored  brown,  the  same 
as  when  they  are  precipitated  from  the  urine  by  an  acid. 

Detection. — Urochrome  is  recognized  by  the  fact  that  it 
is  precipitated  from  its  solutions  by  ammonium  sulphate, 
and  that  when  it  is  decomposed  by  acids,  it  furnishes  a 
brown  or  black  substance.  It  is  also  distinguished  by  its 
color  and  spectrum. 

Urochrome  is  isolated,  according  to  Garrod,  by  saturating 
the  urine  with  ammonium  sulphate,  and  extracting  the  pre- 
cipitate with  absolute  alcohol.  According  to  Thudichum, 
it  is  best  isolated  by  first  precipitating  the  urine  with  a  mix- 
ture of  barium  hydrate  and  acetate,  and  then  treating  the 
filtrate  with  lead  acetate  and  ammonia.  ^ 

1  See  Neubauer  and  Vogel,  "Analyse  des  Harns,"  Bd.  I,  1898,  S.  508. 


94 


ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 


Uroerythrin. — This  substance  is  a  constituent  of  normal 
urine,  and  is  usually  present  only  in  small  quantities.  It 
has  been  termed  rosacic  acid  by  Prout,  and  piirpiirin  by 
Golding  Bird. 

Uroerythrin  is  free  from  iron,  and  when  isolated,  is  amor- 
phous and  of  a  brick-red  color.  It  is  soluble  in  amyl  alco- 
hol, slightly  soluble  in  acetic  ether  and  absolute  alcohol, 
and  very  difficultly  soluble  in  water.  Its  solution  in  alco- 
hol soon  decomposes.  It  is  also  decomposed  by  both  oxi- 
dizing and  reducing  agents.  Uroerythrin  does  not  occur 
in  the  urine  as  a  chromogen.  When  a  urine  is  saturated 
with  ammonium  sulphate  or  chloride,  uroerythrin  is  pre- 
cipitated with  the  ammonium  urate.  Its  solutions  are  not 
fluorescent.  It  is  extracted  from  a  reddish  urate  sediment 
by  boiling  alcohol. 

Uroerythrin  in  dilute  solutions  shows  two  ill-defined  ab- 


C  I>  £    b 

/O     iO    30     W     ^p     eO     70    80    90     (00   ffO 


'JO  m  /so  m  m 


Fig.  12. — Spectrum  of  uroerythrin  (after  Neubauer  and  Vogel). 


sorption  bands,  one  with  its  left  border  midway  between  D 
and  E,  its  right  border  inclosing  E  {JD  yo  E — E  1 3  E),  and 
the  other  band  with  its  left  border  to  the  right  of  b,  and  its 
right  border  inclosing  F  {E  44  E — E  9  G).  (Fig.  12.) 
The  right  band  is  somewhat  darker  than  the  left,  the  light 
space  between  the  two  being  rather  ill  defined. 

Uroerythrin,  for  the  most  part,  exists  in  the  urine  in 
chemic  combination  with  uric  acid.  It  not  only  gives  a 
yellow,  or  yellowish-red,  color  to  uric  acid  crystals,  but 
also  colors  a  urate  sediment  pink  or  brick-red. 

Clinically,  uroerythrin  is  increased  in  acute  febrile  dis- 
eases, such  as  pneumonia,  influenza,  typhoid  fever,  malaria, 
acute  articular  rheumatism,  etc.  ;  in  diseases  of  the  liver, 
especially  those  in  which  there  is  a  disturbance  in  the  circu- 
lation ;  in  cirrhosis  of  the  liver  following  the  excessive  use 


UROROSEIN.  95 

of  alcohol  ;  and  in  chronic  diseases  of  the  heart  and  lungs. 
An  increase  of  uroerythrin  is  usually  accompanied  by  an 
increase  of  urobilin. 

Detection. — A  deposit  of  amorphous  urates  having  a 
pink  or  reddish  color  shows  the  presence  of  uroerythrin. 
On  the  addition  of  an  alkaline  hydrate  its  solution  is  imme- 
diately colored  dark  green.  An  amyl-alcohol  solution  of 
uroerythrin,  obtained  by  shaking  the  urine  with  amyl  alco- 
hol, shows  the  characteristic  absorption  bands.  It  is  iso- 
lated by  saturating  the  urine  with  ammonium  chloride. 

Urorosein. — Urorosein  does  not  occur  in  the  urine  as 
such,  but  as  a  chromogen,  which,  upon  the  addition  of 
mineral  acids,  is  gradually  broken  up,  a  rose-red  color  re- 
sulting. According  to  Robin,  this  substance  is  present  in 
very  small  amounts  in  every  normal  urine,  and  in  much 
larger  quantities  in  certain  diseased  conditions. 

Urorosein  dissolves  in  water  with  a  resulting  red  color  ; 
also  in  dilute  mineral  and  many  of  the  organic  acids  ;  in 
alcohol  and  amyl  alcohol.  It  is  extracted  from  its  aqueous 
solution  by  amyl  alcohol,  but  not  by  ether,  chloroform, 
benzol,  or  carbon  disulphide.  Its  alcoholic  solution  shows 
a  sharp  and  narrow  absorption  band  between  D  and  E  [D 
48  E).  Ammonia,  hydrates  of  the  fixed  alkalies,  and  alka- 
line carbonates  immediately  decolorize  the  red  solution. 

The  chromogen,  according  to  Robin,  crystallizes  in  color- 
less transparent  needles  when  its  concentrated  alcoholic 
solution  is  precipitated  with  ether.  These  crystals  are 
readily  soluble  in  alcohol  and  water,  but  not  in  ether  or 
chloroform.     It  is  incompletely  precipitated  by  lead  acetate. 

Clinically,  urorosein  is  increased  in  the  urine  in  diseases 
of  the  lungs  (tuberculosis),  pernicious  anemia,  and  in  cases 
of  marked  chlorosis.  It  is  also  increased  in  diabetes  mel- 
litus,  osteomalacia,  typhoid  fever,  carcinoma  of  any  of  the 
abdominal  viscera,  appendicitis,  nephritis,  and  especially 
in  diseases  of  the  stomach.  It  is  increased  by  vegetable 
food. 

Detection. — (i)  To  10  c.c.  of  the  urine  add  15  drops 
of  concentrated  hydrochloric  acid,  and  if  the  urine  be  rich 
in  urorosein,  a  rose-red  color  appears  in  the  cold  in  about 
ten  minutes  ;  the  color  appears  more  quickly  when  the 
mixture  is  heated  to  70°  C.  (Robin).  (2)  Take  from  50  to 
100  c.c.  of  the  urine  and  add  from  5  to  10  c.c.  of  25  per 
cent,  sulphuric  acid.      A   reddish  or  rose-red  color  appears 


96  ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

in  a  few  minutes.  If  this  colored  mixture  is  then  shaken 
with  amyl  alcohol,  the  coloring-matter  is  removed  (Nencki 
and  Sieber). 

The  spectroscopic  examination  of  the  amyl-alcohol  ex- 
tract is  indispensable  for  the  certain  detection  of  urorosein. 


OTHER  ORGANIC  CONSTITUENTS  OF  THE  URINE. 

A  number  of  organic  constituents,  in  addition  to  those 
already  described,  may  occur  in  small  quantities  in  the  urine. 
We  may  divide  these  into  the  following  groups  : 

1.  Nonnitrogenous  acids  :  oxalic,  lactic,  and  succinic 
acids. 

2.  Fatty  acids. 

3.  Glycerophosphoric  acid  (?). 

4.  Carbohydrates  :  dextrose  (see  p.  145)  and  animal  gum. 

5.  Ferments  :  pepsin,  trypsin. 

6.  Mucin. 

Oxalic  Acid  (QH^OJ. — Oxalic  acid  is  usually,  and  per- 
haps always,  a  constituent  of  the  urine  in  health,  but  is 
present  in  very  small  amounts  (as  high  as  0.02  gram  in 
twenty -four  hours).  Under  pathologic  conditions  it  appears 
in  increased  quantities  in  diabetes  mellitus,  organic  diseases 
of  the  liver,  and,  indeed,  in  all  conditions  in  which  the  oxi- 
dizing power  of  the  system  is  decidedly  interfered  with,  as 
in  various  diseases  of  the  heart  and  lungs. 

Oxalic  acid  crystallizes  with  two  molecules  of  H,0  in 
colorless,  rhombic  prisms,  which  are  readily  soluble  in  water 
and  alcohol. 

The  greater  part  of  the  oxalic  acid  taken  into  or  formed 
in  the  body  exists  in  the  form  of  a  salt  of  calcium — calcium 
oxalate. 

Calcium  Oxalate. — This  salt  crystallizes  in  two  different 
forms  according"  to  the  number  of  molecules  of  water  it 
contains — /.  c,  crystals  belonging  to  the  monoclinic  system 
— C2CaO^,  H,,0  (small  plates) — and  those  belonging  to  the 
tetragonal  system — C2CaO^,3H.,0  (octahedra,  etc.).  The 
monoclinic  crystals  are  seen  when  the  salt  rapidly  separates 
from  a  concentrated  solution  ;  the  amorphous  precipitate  of 
calcium  oxalate  apparently  has  the  same  chemic  composi- 
tion. The  tetragonal  crystals  are  seen  when  the  salt  slowly 
separates  from  dilute  acid  solutions. 

For  a  further  consideration  of  this  subject  see  page  217. 


FERMENTS.  97 

Lactic  Acid  (C^HgOj,)  is  not  a  constituent  of  normal  urine. 
Liebig  was  unable  to  detect  the  slightest  trace  of  it  in  41,  42, 
and  56  liters  of  healthy  urine.  It  does  not  appear  in  the  urine 
after  the  administration  of  sodium  lactate  (Nencki  and  Sieber). 
It  has  been  found  in  the  urine  in  combination  with  bases  in  cases 
of  acute  yellow  atrophy  and  marked  cirrhosis  of  the  liver,  trichi- 
nosis, phospliorus-poisoning,  and  after  severe  muscular  exertion. 
According  to  Colasanti  and  Moscatelli,  it  occurs  in  the  urine  as 
sarcolactic  acid. 

Sarcolactic  acid  consists  of  a  colorless,  odorless,  syrupy  fluid, 
soluble  in  water,  alcohol,  and  ether;  it  is  nonvolatile.  The  free 
acid  rotates  the  plane  of  polarizedlight  slightly  toward  the  right, 
while  solutions  of  its  salts  rotate  the  plane  slightly  toward  the 
left  (Wislicenus).  Lactic  acid  is  monobasic;  it  combines  with 
bases  to  form  salts,  of  which  zinc  lactate  is  the  most  important. 
Nearly  all  of  its  salts  are  soluble. 

For  the  detection  of  lactic  acid  see  Neubauer  and  Vogel, 
"  Analyse  des  Harns,"  Bd.  i,  1898,  S.  183. 

Succinic  Acid  (C^HgO^)  has  been  occasionally  found  in  the 
urine.  Under  ordinary  conditions  it  probably  exists  in  the 
urine  chiefly  in  combination  with  sodium — sodium  succinate. 
Succinic  acid  has  been  found  in  the  urine  especially  after  the 
ingestion  of  asparagus  and  asparagin.  Baumann  failed  to  find 
it  after  the  ingestion  of  sodium  succinate. 

Fatty  Acids. — These  consist  of  acetic,  butyric,  formic,  and 
propionic  acids.  They  are  apparently  free  in  the  urine,  and 
present  only  in  mere  traces  (0.008  gram  per  diem).  They  can 
be  increased  to  0.9-1.5  gram  by  treating  the  urine  with  oxidiz- 
ing agents  (v.  Jaksch^).  The  amount  of  fatty  acids  also 
increases  during  the  period  of  the  ammoniacal  fermentation 
(Salkowski  2).  In  certain  febrile  conditions  they  are  increased 
to  0.6  gram,  and  in  certain  liver  diseases  may  go  as  high  as  one 
gram  per  diem.     This  condition  is  called  lipaciduria  by  v.  Jaksch. 

Ferments. — Pepsin. — Several  observers  (Briicke,  Sahli, 
Leo,  and  others)  have  found  pepsin  in  the  urine.  The  fol- 
lowing is  an  alDstract  of  Leo's  ^  work  on  the  subject  : 
"  Small  pieces  of  fibrin  soaked  in  the  urine  absorb  the  pep- 
sin, and  on  removing  them  to  o.  i  per  cent,  hydrochloric 
acid,  they  are  rapidly  digested.  Control  experiments  with 
fibrin  not  previously  soaked  in  urine  gave  negative  results. 
The  morning  urine  was  found  to  be  richest  in  pepsin." 

Neumeister  and  Stadelmann  have  both  shown  that  the 
ferment  in  the  urine  is  true  pepsin. 

1  "Zeitschr.  f.  physiol.  Chem.,"  X,  536.  2  Ibid.,  xni,  264. 

3  "Pfliiger's  Archiv,"   xxxvn,  223,  and  xxxix,  246. 
7 


98      ■      ORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

Trypsin. — This  ferment  is  probably  absent  from  normal  urine, 
although  Sahli  claims  to  have  found  it. 

Mucin. — Much,  discussion  has  arisen  as  to  whether  the  sub- 
stance that  is  nearly  always  present  in  very  minute  quantities  in 
the  urine  is  mucin  or  really  nucleo-albuniin.  It  is  considered 
by  some  observers  to  be  the  chief  constituent  of  the  mucus  de- 
rived from  the  muciparous  glands  of  the  urinary  tract  below  the 
kidneys.  Further,  that  it  occurs  in  normal  urine  as  a  viscid, 
slimy  substance,  which  is  precipitated  by  the  vegetable  acids, 
especially  acetic  acid  ;  also  by  alcohol ;  that  it  is  free  from 
phosphorus,  and,  when  boiled  with  dilute  acids,  yields  a  sub- 
stance that  reduces  alkaline  solutions.  More  recent  observers 
consider  it  to  be  nucleo-albumin,  and  at  the  present  time  this 
theory  is  most  tenable.  (Seep.  140.)  The  question,  however, 
is  unsettled,  and  needs  further  investigation. 


CHAPTER  III. 

INORGANIC  CONSTITUENTS  OF  NORMAL 
URINE. 

The  principal  inorganic  constituents  of  the  urine  are  the 
chlorides,  phosphates,  and  sulphates,  which  are  in  combina- 
tion with  sodium,  potassium,  ammonium,  calcium,  and  mag- 
nesium ;  also  traces  of  carbonates  of  the  alkalies.  There 
are  also  traces  of  iron,  fluorine,  and  silicic  acid,  as  well  as 
free  gases,  including  carbonic  acid,  nitrogen,  and  oxygen. 

The  combined  quantities  of  these  various  substances 
amount  to  between  nine  and  twenty-five  grams  in  twenty- 
four  hours. 

CHLORIDES. 

Chlorine  exists  in  the  urine  chiefly  as  sodium  chloride, 
although  small  amounts  are  in  combination  with  potassium 
and  ammonium.  The  chlorides,  next  to  urea,  constitute 
the  chief  solid  constituent  of  the  urine.  They  are  derived 
from  the  food, — that  is,  the  sodium  chloride  ingested  with 
the  food, — and  under  normal  conditions  practically  all  of 
this  salt  ingested  is  eliminated  in  the  urine  in  an  equivalent 
amount. 

The  quantity  of  sodium  chloride  in  the  twenty-four-hour 
urine  is  normally  between  lo  and  20  grams,  and,  calculated 
as  chlorine,  amounts  to  between  8  and  1 2  grams.  A  person 
ingesting  food  unusually  rich  in  sodium  chloride  may  elimi- 
nate more  than  20  grams  (NaCl),  and  the  quantity  may 
even  reach  40  or  50  grams  in  the  twenty-four  hours.  On 
the  other  hand,  if  the  amount  of  nourishment  is  diminished, 
a  decrease  in  the  elimination  of  the  chlorides  is  observed. 
If  this  is  carried  to  the  point  of  starvation,  the  chlorides 
almost  entirely  disappear  from  the  urine,  the  traces  remain- 
ing being  derived  from  the  tissues  and  fluids  of  the  body. 
The  latter  retain   tenaciously  a   certain  amount  of  sodium 

99 


100        INORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

chloride,  and  if,  following  a  period  of  starvation,  food  con- 
taining sodium  chloride  is  again  taken,  not  all  appears  in 
the  urine,  but  a  portion  is  retained  in  the  body  until  the 
original  equilibrium  is  restored.  A  similar  retention  may 
be  observed  for  a  few  days  following  the  ingestion  of  large 
quantities  of  water,  which,  under  ordinary  conditions,  causes 
an  increased  elimination  of  chlorides. 

An  incrc(7scd  quantity  of  chlorine  is  due  to  an  abundance 
of  NaCl  in  the  food,  and  is  of  no  clinical  importance.  In 
diabetes  insipidus,  however,  the  increase  of  chlorine,  which 
may  reach  thirty  grams  or  more,  is  obtained  at  the  expense 
of  the  body-fluids,  and  is,  therefore,  associated  with  marked 
emaciation.  A  dhni)mtio)i  in  the  quantity  of  chlorine  is  in 
many  instances  of  the  greatest  clinical  importance.  Such  a 
diminution  is  often  the  result  of  disease,  and  not  dependent 
entirely  on  a  diminished  quantity  of  salt  ingested,  although 
a  low  diet,  naturally,  has  some  effect  on  the  quantity  of 
chlorine  eliminated. 

Clinical  Significance. — The  chlorides  are  diminished  in 
the  acute  stage  of  all  acute  diseases,  and  especially  those 
associated  with  a  serous  exudation  or  transudation  (dropsy), 
vomiting,  or  diarrhea.  One  of  the  most  important  examples 
of  this  is  pneumonia,  in  the  acute  stage  of  which,  on 
account  of  the  serous  exudation,  the  chlorine  is  very  low  or 
may  even  be  entirely  absent  from  the  urine.  As  soon  as 
convalescence  commences  and  the  serous  exudation  begins 
to  be  absorbed,  the  chlorine  reappears  or  gradually  increases 
until  it  may,  in  a  few  days,  exceed  the  normal  temporarily. 
The  test  for  chlorides  is,  therefore,  of  definite  clinical  value 
in  determining  the  progress  of  the  pneumonic  process.  The 
quantity  of  chlorine  in  the  urine  is  very  important  in  the 
differential  diagnosis  between  acute  meningitis  and  typhoid 
fever,  the  former  being  attended  with  a  serous  exudation, 
and  hence  a  inm-kcd  diminution  in  the  chlorides,  while  in 
the  latter  they  are  only  moderately  diminished.  The  chlorine 
is  markedly  diminished  or  absent  in  cholera,  pyemia,  and 
puerperal  fever,  and  also  much  diminished  in  acute  articular 
rheumatism. 

In  the  convalescent  stage  of  most  acute  diseases  the 
chlorine  gradually  rises  to  normal,  but  is  dependent  chiefly 
on  the  appetite. 

The  chlorides  are  diminished  in  all  chronic  diseases,  more 
particularly  in  those  attended  with  dropsy,  when  they  may 


CHLORIDES.  101 

be  absent  from  the  urine.  In  the  chronic  diseases  without 
exudation  or  transudation  the  diminution  in  the  amount  of 
chlorine  is  in  proportion  to  the  amount  of  sodium  chloride 
taken  with  the  food — in  other  words,  the  quantity  of 
chlorine  may  be  looked  upon  as  a  measure  of  the  appe- 
tite. If  at  any  time  during  the  course  of  a  chronic  disease 
accompanied  by  dropsy  the  fluid  be  absorbed,  the  quantity 
of  chlorine  in  the  urine  slowly  rises  to  near  the  normal,  but 
only  rarely  does  it  exceed  the  normal,  since  the  absorption 
of  the  serous  fluid  is  usually  very  gradual. 

Detection. — The  following  test,  which  depends  upon  the 
precipitation  of  the  chlorine  by  nitrate  of  silver,  can  be 
readily  applied  for  the  detection  and  approximate  estimation 
of  chlorides  in  the  urine  : 

Take  one-half  of  a  wine-glass  of  urine,  underlie  with  a 
third  as  much  concentrated  nitric  acid  in  the  same  manner 
as  in  the  nitric  acid  test  for  albumin.  (See  p.  122.)  Then 
add  one  drop  of  a  solution  of  silver  nitrate, — one  part  of 
silver  nitrate  and  eight  parts  of  water, — and  if  chlorides  be 
present,  a  precipitate  of  silver  chloride  is  formed.  If  the 
relative  proportion  of  chlorides  is  normal  or  increased,  a 
solid  compact  ball  of  silver  chloride  is  obtained,  which  falls 
to  the  surface  of  the  nitric  acid.  If  the  relative  proportion 
is  diminished,  however,  instead  of  forming  a  solid  ball  the 
silver  chloride  precipitate  spreads  out  or  becomes  diffused  to 
a  greater  or  less  extent  through  the  layer  of  urine. 

This  same  test  can  also  be  applied  by  adding  to  one-half 
of  a  wine-glass  of  urine  one  or  two  drops  of  concentrated 
nitric  acid,  stirring  the  mixture,  and  adding  one  drop  of  the 
solution  of  silver  nitrate  (prepared  as  directed).  If  the  result- 
ing precipitate  quickly  falls  to  the  bottom  of  the  glass  in  a 
solid,  flaky  mass  and  does  not  tend  to  diffuse  through  the 
urine,  the  chlorides  are  normal  or  increased  ;  if  diffused, 
they  are  diminished. 

If  the  urine  contains  more  than  a  trace  of  albumin,  it 
must  be  removed  by  heat  before  the  test  is  applied,  for  the 
following  reasons:  (i)  The  precipitate  or  ball  of  silver 
chloride  can  not  be  distinctly  seen  because  of  the  cloud  of 
precipitated  albumin  ;  (2)  the  silver  and  albumin  combine  to 
form  the  albuminate  of  silver,  thus  modifying  the  inferences 
to  be  deduced  from  the  test. 

Quantitative  Tests. — (a)  Mohr's  Method. — Precipita- 
tion by  silver  nitrate. 


102        INORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

The  following  solutions  are  necessary  : 

1.  Standard  Silver  Nitrate  Solution:  Dissolve  29.075 
grams  of  fused  silver  nitrate  in  distilled  water,  and  make 
the  whole  quantity  up  to  exactly  one  liter  (1000  c.c).  One 
cubic  centimeter  of  this  solution  is  equivalent  to  o.oi  gram 
of  sodium  chloride,  or  0.006065  gram  of  chlorine. 

2.  A  solution  of  neutral  potassium  chromate,  made  by  dis- 
solving one  part  of  the  chlorine-free  salt  in  five  parts  of  water. 

Process. — Take  10  c.c.  of  urine  ;  dilute  with  50  c.c.  of 
distilled  water  ;  add  to  this  8  or  10  drops  of  potassium 
chromate  solution.  Drop  into  this  mixture  from  a  burette 
the  standard  nitrate  of  silver  solution.  The  chlorine  com- 
bines with  the  silver  to  form  silver  chloride — a  white  precip- 
itate. When  all  the  chlorine  is  precipitated,  silver  chro- 
mate (red  in  color)  forms,  but  not  while  any  chloride 
remains  in  solution.  The  silver  nitrate  solution  must,  there- 
fore, be  added  until  a  pink  tinge  appears.  Read  off  the 
quantity  of  standard  solution  of  silver  used,  subtract  i  c.  c. 
for  correction  (see  below),  and  calculate  therefrom  the 
quantity  of  chlorine,  or  sodium  chloride,  in  the  10  c.c.  of 
urine  tested.  From  this  deduce  the  percentage,  or  the 
total  number  of  grams  in  the  twenty-four-hour  urine.  For 
example,  suppose  that,  after  deducting  i  c.c.  for  correction, 
exactly  10.5  c.c.  of  the  standard  silver  nitrate  solution 
were  used.  Since  i  c.c.  of  this  solution  is  equivalent  to 
0.006065  gram  of  chlorine,  10.5  X  0.006065  =0.0636825 
gram,  or  the  amount  of  chlorine  in  the  10  c.c.  of  urine 
used.      Then  the  twenty-four-hour  urine — say  1500  c.c. — 

contains  0.0636825  X  -^=9-55  grams. 

Precautions  and  Corrections. — If  the  urine  contains  al- 
bumin, it  must  be  removed  by  means  of  heat  and  acetic 
acid. 

The  phosphate  of  silver  is  not  precipitated  in  this  test,  as 
the  silver  salts  of  hydrochloric,  chromic,  and  phosphoric 
acids  are  precipitated  in  the  following  order :  chloride, 
chromate,  and,  finally,  the  phosphate. 

A  highly  colored  urine  may  give  rise  to  difficulty  in  de- 
tecting the  pink  tinge  of  the  chromate  of  silver.  This  is 
overcome  by  diluting  the  urine  to  a  greater  extent  than  in 
the  directions  given.  It  is  not  always  necessary  to  dilute 
a  pale-colored  urine  to  the  extent  previously  stated,  the  addi- 
tion of  20  to  30  c.c.  of  water  often  being  sufficient. 


CHLORIDES.  103 

One  cubic  centimeter  should  always  be  subtracted  from 
the  total  number  of  cubic  centimeters  of  silver  nitrate  solu- 
tion used,  as  the  urine  contains  small  quantities  of  certain 
compounds  more  easily  precipitable  than  the  chromate  of 
silver.  To  obviate  this  error,  Sutton  lias  advised  the  foi- 
lenving  modification  of  Alohr's  test :  Take  lo  c.c.  of  urine 
in  a  thin  porcelain  dish,  and  add  i  gram  of  pure  ammonium 
nitrate.  The  whole  is  then  evaporated  to  dryness,  and 
gently  heated  over  a  small  flame  to  low  redness  until  all 
vapors  are  dissipated  and  the  residue  becomes  white.  It  is 
then  dissolved  in  a  small  quantity  of  water,  and  the  carbon- 
ates produced  by  combustion  of  the  organic  matter  neutral- 
ized by  dilute  acetic  acid.  A  few  grains  of  pure  carbonate 
of  calcium  are  added  to  remove  all  free  acid,  and  then  one  or 
two  drops  of  a  solution  of  potassium  chromate.  The  mix- 
ture is  then  titrated  with  decinormal  silver  solution  (16.966 
grams  of  silver  nitrate  to  the  liter)  until  the  pink  color 
appears.  Since  each  cubic  centimeter  of  the  silver  solution 
represents  0.005837  gram  of  sodium  chloride,  the  quantity 
of  sodium  chloride,  or  chlorine,  can  be  readily  calculated. 

The  results  obtained  by  direct  titration  of  the  urine  with 
a  standard  solution  of  silver  nitrate  can  not  be  considered 
absolutely  accurate,  since  uric  acid,  xanthin  bases,  sulpho- 
cyanides,  sulphites,  coloring-matters,  etc.,  are  precipitated 
with  the  silver  chloride  before  the  end-reaction  appears. 
To  obviate  such  errors,  Neubauer  and  Salkowski  have  ad- 
vised the  following  process  : 

Neubauer-Salkowski  Method. — The  necessary  solu- 
tions are  to  be  prepared  according  to  the  directions  given 
under  Mohr's  method. 

Take  10  c.c.  of  urine  in  a  small  platinum  or  porcelain 
crucible  ;  add  one  gram  of  sodic  carbonate  that  is  free  from 
chlorine,  and  i  or  2  grams  of  chlorine-free  potassium  nitrate, 
and  evaporate  to  dryness  at  100°  C.  Heat  over  a  free 
flame — at  first  gently,  later  strongly — until  the  molten  mass 
is  perfectly  white.  Dissolve  the  white  residue  in  distilled 
water,  and  transfer  the  solution  to  a  small  flask.  To  this 
alkaline  solution  add  dilute  nitric  acid,  drop  by  drop,  until 
faintly  acid,  and  then  neutralize  again  with  chlorine-free 
sodic  carbonate.  Add  a  few  drops  of  the  solution  of  potas- 
sium chromate  to  the  mixture,  and  allow  the  standard  solu- 
tion of  silver  nitrate  to  flow  from  a  burette  into  the  mixture 
in  the  flask,  until  the  first  appearance  of  a  permanent  pink 


104        INORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

tinge  (end-reaction).  Read  the  number  of  cubic  centimeters 
of  standard  solution  of  silver  used,  and  calculate  therefrom 
the  quantity  of  chlorine  or  sodium  chloride  in  the  lo  c.c. 
of  urine  tested. 

Volhard  and  Falck  Method. — This  method  depends 
upon  the  action  of  soluble  sulphocyanides  with  solutions  of 
silver  and  ferric  salts.  Soluble  sulphocyanides  produce  in 
silver  solutions  a  white  precipitate  of  sulphocyanide  of  silver, 
which  is  insoluble  in  dilute  nitric  acid.  A  like  precipitate 
of  sulphocyanide  of  silver  with  a  solution  of  nitrate  of  silver 
is  given  by  the  blood-red  solution  of  sulphocyanide  of  iron, 
and  the  color  of  the  latter  at  last  completely  disappears. 
If,  therefore,  a  solution  of  sulphocyanide  of  potassium  be 
added  to  an  acid  solution  of  nitrate  of  silver  to  which  a 
little  ferric  sulphate  has  been  added,  every  drop  of  the 
sulphocyanide  solution  at  first  produces  a  blood-red  cloud, 
which,  however,  quickly  disappears  on  stirring,  while  the 
fluid  becomes  milk-white.  It  is  not  until  all  the  silver  is 
precipitated  that  the  red  color  of  the  sulphocyanide  of  iron 
remains  permanent  and  the  end  of  the  process  is  reached. 

The  following  solutions  are  necessary  : 

/.  Standard  solution  of  sil^'cr  nitrate,  made  according  to 
directions  given  under  Mohr's  method.  One  cubic  centi- 
meter is  equivalent  to  0.006065  gram  (6.065  milligrams) 
of  chlorine,  or  0.0 10  gram  (10  milligrams)  of  sodium 
chloride. 

2.  Solution  of  Ferric  Oxide. — A  cold,  saturated  solution 
of  ciystallized  ferric  alum  free  from  chlorine,  or  a  solution 
of  ferric  sulphate  that  contains  50  grams  of  oxide  of  iron 
to  the  liter. 

J.  Standard  Solution  of  Potassium  Sidphocyanide. — Since 
potassium  sulphocyanide  can  not  be  accurately  weighed, 
because  of  its  hygroscopic  property,  it  is  necessary  to  stand- 
ardize by  titrating  with  a  standard  solution  of  silver  nitrate. 
Dissolve  10  grams  of  potassium  sulphocyanide  in  a  little 
less  than  a  liter  of  distilled  water,  and  place  a  portion  of 
this  in  a  burette.  Take  10  c.c.  of  the  standard  silver  solu- 
tion, place  in  a  beaker,  add  5  c.c.  of  the  iron  solution,  and 
then  pure  nitric  acid,  drop  by  drop,  until  the  mixture  is 
colorless.  Then  allow  the  sulphocyanide  solution  to  flow 
in  from  the  burette  until  the  fluid  has  a  permanent  red  color, 
the  first  appearance  of  which  indicates  the  end-reaction — 
that  is,  when  all  of  the  silver  is  precipitated  as  silver  sulpho- 


CHLORIDES.  105 

cyanide,  the  next  drop  gives  a  permanent  red  color,  due  to 
the  precipitation  of  the  sulphocyanide  of  iron.  If,  for  ex- 
ample, to  lo  c.c.  of  the  silver  solution  9.6  c.c.  of  the  potas- 
sium sulphocyanide  solution  have  been  used  before  the  red 
color  is  permanent,  960  c.c.  are  measured  off,  and  diluted 
with  40  c.c.  of  distilled  water  to  make  a  liter.  Titrate  once 
more,  in  order  to  be  sure  that  the  strength  of  the  two  solu- 
tions— standard  silver  and  potassium  sulphocyanide  solu- 
tions— is  equivalent. 

Process. — Take  10  c.c.  of  urine,  add  i  or  2  grams  of 
potassium  nitrate  free  from  chlorine,  and  evaporate  to  dr>'- 
ness  on  a  water-bath.  The  residue  is  then  heated  over  a 
free  flame — at  first  gently,  afterward  strongly — until  the 
carbon  is  completely  oxidized  and  the  residue  is  a  white 
mass.  Since  the  nitrous  acid  formed  in  this  process  pre- 
vents the  end-reaction,  the  fused  mass  is  dissolved  in  water, 
acidulated  with  nitric  acid,  and  then  the  chlorine  precipi- 
tated with  an  excess  of  the  standard  solution  of  silver. 
After  this  mixture  has  been  warmed  on  a  water-bath  for  a 
time  to  remove  completely  the  nitrous  acid,  it  is  allowed  to 
cool.  Then  5  c.c.  of  the  iron  solution  are  added  ;  and, 
finally,  the  potassium  sulphocyanide  solution,  until  the  ex- 
cess of  the  silver  added  is  precipitated,  which  is  known  by 
the  permanent  red  color  of  the  mixture.  The  difference  be- 
tween the  number  of  cubic  centimeters  of  the  silver  and 
sulphocyanide  solutions  corresponds  to  the  chlorine  con- 
tained in  the  urine.  If,  for  instance,  at  first  15  c.c.  of  the 
silver  solution  were  added  to  10  c.c.  of  urine,  and  5  c.c.  of 
the  sulphocyanide  solution  were  required  to  titrate  back  the 
excess,  the  amount  of  chlorine  in  the  urine  would  corre- 
spond to  15  —  5  =  10  c.c.  of  the  silver  solution. 

(b)  Purdy's  Method,  by  the  Electric  Centrifuge. — 
The  percentage  tubes  of  the  Purdy  electric  centrifuge  are 
filled  to  the  lo-c.c.  mark  with  the  urine  to  be  tested; 
fifteen  (15)  drops  of  nitric  acid  are  added  to  prevent  precipi- 
tation of  the  phosphates  (if  the  specific  gravity  be  very  high, 
20  to  30  drops  should  be  added),  and  then  the  tubes  are 
filled  to  the  15-c.c.  mark  with  a  strong  solution  of  nitrate 
of  silver  ( i  :  8).  The  tubes  are  next  closed,  and  inverted 
several  times,  until  the  urine  and  the  reagents  are  thoroughly 
mingled.  The  tubes  are  then  placed  in  the  centrifuge,  and 
revolved  at  the  rate  of  1000  revolutions  a  minute  for 
three   successive   periods  of  five    minutes   each,   when   the 


106        INORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

quantity  in  bulk  percentage  may  be  read  off  from  the  grad- 
uated scale  on  the  sides  of  the  tubes.  Purdy  has  found 
that  the  bulk  percentage  of  chlorides  in  normal  urine  thus 
obtained  ranges  from  lo  to  12  per  cent. 

By  a  comparison  of  the  bulk  percentages  of  chlorides 
Avith  the  volumetric  determinations  of  the  same  the  author 
has  been  able  to  obtain,  from  a  large  number  of  observa- 
tions, a  standard  of  percentage  by  weight.  He  has  found 
that  each  ^  of  a  c.c.  of  precipitate,  calculated  as  chlorine, 
is  equivalent  to  0.123  P^^'  cent,  by  weight. 


PHOSPHATES. 

Phosphoric  acid  in  the  urine  occurs  in  the  form  of  two 
classes  of  phosphates  : 

1 .  Earthy  Phosphates  :  phosphates  of  calcium  and  mag- 
nesium, the  former  being  the  more  abundaht. 

2.  Alkaline  Phosphates  :  phosphates  of  sodium  and  po- 
tassium, the  former  being  the  more  abundant. 

The  earthy  phosphates,  which  consist  of  the  phos- 
phates of  the  alkaline  earths, — calcium  and  magnesium, 
— are  insoluble  in  water,  but  soluble  in  acids.  In  an  acid 
urine  they  are  in  the  form  of  acid  phosphates,  which  are 
in  solution.  Occasionally,  a  crystalline  deposit  of  acid 
calcium  phosphate  (see  p.  216)  having  the  composition 
CaHPO^  +  2H2O  (Hassal,  Stein)  separates  from  a  faintly 
acid  urine. 

In  an  alkali)ic  urine  the  acid  phosphates  of  magnesium 
and  calcium  are  converted  to  normal  phosphates,  and  are 
precipitated  as  a  heavy,  whitish  sediment,  frequently  termed 
anwrpJioiis  phosphates.  A  similar  phosphatic  precipitate  is 
often  obtained  when  a  faintly  acid,  neutral,  or  alkaline  urine 
is  heated,  owing  to  the  conversion  of  the  acid  phosphate  to 
normal  phosphate,  which  is  precipitated,  and  the  superphos- 
phate, which  remains  in  solution  :  / 

/ 
4CaHPO,  =  CaH^2PO^  +  Ca32PO,. 

This  phenomenon  is  a  frequent  source  of  error  in  testing 
for  albumin  in  urine  by  heat.  If,  upon  heating,  such  a  pre- 
cipitate appears,  it  may  be  readily  distinguished  from  the 
precipitate  of  albumin  by  the  addition  of  a  few  drops  of 
acetic  acid,  which  quickly  dissolves  the  earthy  phosphates. 
When  a  urine  becomes  aininoniacal,  the  phosphate  of  mag- 


PHOSPHATES.  107 

nesium  combines  chemically  with  ammonia  to  form  the 
aviuio)iio-)iicxgiicsium plwspJiatc ,  or  "  triple  phosphate,"  which 
is  in  crystalline  form.      (See  p.  215.) 

The  alkaline  phosphates  consist  chiefly  of  the  phos- 
phates of  sodium  and  potassium,  which,  unlike  the  earthy 
phosphates,  are  soluble  in  water  and  alkalies.  The  sodium 
salt — monosodic  acid  phosphate  (the  disodic  acid  phosphate 
is  also  sometimes  present) — is  much  more  abundant  than 
the  potassium  salt,  and,  as  previously  stated,  it  is  to  this  com- 
pound that  the  acidity  of  the  urine  is  chiefly  due.  The 
alkaline  phosphates  form  the  chief  bulk  of  the  phosphates 
of  the  urine,  being  in  excess  of  those  combined  with  the 
alkaline  earths,  the  proportion  being  between  i  ^  and  2  of 
the  former,  to    i  of  the  latter. 

The  phosphoric  acid  of  the  urine  is  derived  partly  from 
the  food  and,  apparently,  partly  from  the  decomposition 
products  of  phosphorus-containing  organic  substances  such 
as  nuclein  and  lecithin. 

The  average  quantity  of  phosphoric  acid  in  the  twenty- 
four-hour  urine,  calculated  as  phosphoric  anhydride  (P.,0.), 
is  from  2.5  to  3.5  grams.  This  quantity  is  subject  to  much 
variation  in  health,  and  on  a  diet  rich  in  earthy  salts  may 
fall  to  only  a  fraction  of  a  gram,  owing  to  the  fact  that  the 
phosphoric  acid  combines  with  the  earthy  salts,  and  is  thus 
prevented  from  being  absorbed. 

Clinical  Significance. — Undei^pathologic  conditions  the 
phosphoric  acid  is  largely  increased  in  the  urine  in  ex- 
tensive diseases  of  the  bones,  as  rickets,  osteomalacia,  dif- 
fuse periostosis,  etc.;  in  destructive  diseases  of  the  lung,  as 
in  pulmonar}^  tuberculosis,  particularly  in  the  early  stages  ; 
in  extensive  diseases  of  the  nervous  tissue,  diseases  of  the 
brain,  in  chorea,  etc. ;  in  acute  yellow  atrophy  of  the  liver  ; 
after  sleep  produced  by  potassium  bromide,  or  chloral  hy- 
drate (Mendel)  ;  and  it  is  temporarily  increased  after  copious 
drafts  of  water. 

Phosphoric  acid  is  diminished  in  acute  diseases,  probably 
because  only  a  small  amount  of  food  is  taken  ;  and  most  of 
the  chronic  diseases,  excepting  those  previously  mentioned  ; 
in  all  diseases  of  the  kidney  ;  in  gout ;  in  pregnancy,  prob- 
ably due  to  the  formation  of  the  fetal  bones  ;  and  also  after 
large  doses  of  chalk,  ether,  or  alcohol. 

The  term  phosphaturia  should  be  restricted  to  indicate 
a  constant  increase  in  the  total  quantity  of  phosphoric  acid 


108        INORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

in  solution  in  the  urine.  The  term  is  frequently  incorrectly 
applied  to  urine  that  has,  constantly,  a  deposit  of  amor- 
phous or  crystalline  phosphates.  Those  pathologic  con- 
ditions in  which  the  urine  contains  an  abnormally  large 
excess  of  phosphates  in  the  twenty-four-hour  urine  may  be 
said  to  be  attended  with  "  phosphaturia." 

A  condition  of  so-called  phosphatic  diabetes  has  been 
described  by  a  few  writers,  in  which  the  urine  is  free  from 
sugar,  but  contains  a  continued  large  excess  of  phosphates. 
The  symptoms  are  not  unlike  those  of  diabetes  :  /.  r.,  large 
daily  quantity  of  urine,  emaciation,  aching  pains  in  the 
lumbar  region,  morbid  appetite,  dry,  harsh  skin,  etc.  Not 
infrequently  this  condition  seems  to  alternate  with  diabetes 
mellitus  :  that  is,  the  symptoms  of  diabetes  continuing,  the 
sugar  disappears  from  the  urine,  and  is  apparently  re- 
placed by  a  ver>'  large  excess  of  the  phosphoric  acid — as 
much  as  lO  grams.  If  the  sugar  reappears,  the  quantity 
of  phosphoric  acid  falls  to  normal  or  even  below  the 
normal. 

Detection.— I.  Earthy  Phosphates. — The  following 
test  serves  for  the  detection  and  appro.ximate  estimation  of 
the  earthy  phosphates  :  Take  a  half  test-tube  of  filtered 
urine,  and  add  sufficient  amnionic  hydrate  to  render  it 
alkaline.  Upon  warming  the  mixture  the  earthy  phosphates 
separate,  and  soon  begin  to  settle  at  the  bottom  of  the 
tube.  If,  after  eighteen  to  twenty-four  hours,  the  deposit 
thus  formed  is  from  %  to  ^  of  an  inch  deep,  the  relative 
proportion  may  be  said  to  be  within  normal  limits  ;  if  less 
than  %  of  an  inch,  diminished  ;  and  if  more  than  i^  of  an 
inch,  increased. 

2.  Alkaline  Phosphates. — The  following  test  may  be 
applied  for  the  detection  and  approximate  estimation  of  the 
alkaline  phosphates  :  After  having  separated  the  earthy 
phosphates  as  directed,  the  mixture  is  filtered.  Take  the 
entire  filtrate  in  another  test-tube,  and  add  about  one  finger- 
breadth  of  magnesia  mixture.  ^  Upon  warming  the  mixture 
a  white  precipitate,  representing  the  alkaline  phosphates, 
occurs,  which,  if  normal,  settles  down  to  between  i^  and 
'i/^  of  an  inch  after  eighteen  to  twenty -four  hours  ;  if  less 
than  )4,  o(  an  inch,  diminished  ;  and  if  more  than  ^  of  an 
inch, increased. 

1  Magnesia  Mixturf.  —  Magnesium  sulphate,  amnionic  hydrate,  am- 
monium chloride,  of  each,  i  part ;   water,  8  parts. 


PHOSPHATES.  109 

Determination  of  Total  Phosphoric  Acid. — The  follow- 
ing test  is  based  upon  the  facts  that  (i)  when  a  solution  of  a 
phosphate  acidulated  with  acetic  acid  is  treated  with  a  solu- 
tion of  uranium  nitrate  or  acetate,  a  precipitate  falls  that  is 
composed  of  uranium  phosphate  ;  (2)  when  a  soluble  salt 
of  uranium  is  added  to  a  solution  of  potassium  ferrocyanide, 
a  reddish-brown  precipitate,  or  color,  is  developed. 

Prepare  the  following  solutions  : 

{a)  A  Standard  Solution  of  Uj'aninni  Nitrate  or  Acetate. — 
Dissolve  exactly  35.5  grams  of  pure  uranium  nitrate  or  ace- 
tate in  distilled  water  sufficient  to  make  1000  c.c;  i  c.c. 
of  this  solution  corresponds  to  0.005  gi'am  of  phosphoric 
anhydride  (Pp,). 

Oftentimes  it  is  not  safe  to  use  these  salts  of  uranium, 
since  they  are  frequently  contaminated  with  uranic  oxides. 
It  then  becomes  necessary  to  prepare  the  standard  solution 
in  the  following  manner  : 

1.  Make  a  standard  solution  of  sodium  phosphate  by  dis- 
solving 10.085  grams  of  the  well-crystallized  salt  in  dis- 
tilled water,  and  dilute  to  a  liter  ;  50  c.c.  then  contain  o.  I 
gram  of  PgO.. 

2.  To  prepare  the  uranium  acetate  or  nitrate  solution, 
dissolve  20.3  grams  of  yellow  uranic  oxide  in  pure  strong 
acetic  acid  to  make  the  acetate,  or  in  pure  concentrated 
nitric  acid  to  make  the  nitrate,  and  dilute  with  distilled  water 
to  nearly  a  liter.  To  determine  the  strength  of  this  solu- 
tion, take  50  c.c.  of  the  standard  solution  of  sodium  phos- 
phate, in  a  glass  evaporating  dish,  add  5  c.c.  of  the  sodium 
acetate  solution  (given  below),  and  proceed  exactly  as  with 
urine  (process,  see  below).  The  quantity  of  uranium  solu- 
tion used  is  then  read  off,  being  that  which  is  necessary  to 
decompose  the  sodium  phosphate,  corresponding  to  o.i 
gram  of  P.,0..  Then  calculate  the  amount  of  distilled 
water  to  be  added  to  make  i  c.c.  correspond  to  0.005  gram 
of  phosphoric  anhydride. 

{b)  Acid  Solution  of  Sodium  Acetate. — Dissolve  100 
grams  of  sodium  acetate  in  800  c.c.  of  distilled  water  ;  add 
100  c.c.  of  30  per  cent,  acetic  acid,  and  finally  dilute  with 
distilled  water  to  1000  c.c. 

{c)  A  saturated  solution  of  potassium  ferrocyanide,  to  be 
used  as  an  indicator. 

Process. — Take  50  c.c.  of  the  urine  in  a  glass  evapo- 
rating dish,  add  5  c.c.  of  the  sodium  acetate  solution,  and 


110        INORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

heat  the  mixture  to  80°  C.  over  a  water-bath.  From  a 
burette,  run  into  the  hot  urine,  drop  by  drop,  the  standard 
solution  of  uranium,  as  long  as  a  precipitate  forms  or  until 
a  drop  of  the  mixture,  removed  by  means  of  a  glass  rod 
and  placed  on  a  porcelain  plate  or  slab,  gives  a  distinct 
brown  color  with  a  drop  of  the  potassium  ferrocyanide  solu- 
tion. When  this  point  is  reached,  the  quantity  of  uranium 
solution  used  from  the  burette  is  read  off.  The  number  of 
cubic  centimeters  used  multiplied  by  0.005  ^^'^^^  gi^^  ^^^^ 
quantity  of  phosphoric  acid  (calculated  as  phosphoric  anhy- 
dride) in  50  c.c.  of  urine,  and  from  this  is  calculated  the 
quantity  in  twenty-four  hours. 

The  reddish-brown  color  which  takes  place  with  the 
solution  of  potassium  ferrocyanide  and  the  mixture,  first 
makes  its  appearance  at  the  time  when  the  uranium  solution 
has  precipitated  all  of  the  phosphoric  acid,  and  the  mixture 
contains  free  uranium. 

CocJiiiieal  tinctia^e  is  highly  recommended  by  Malot  and 
Mercier  as  an  indicator,  instead  of  the  potassium  ferro- 
cyanide. The  tincture  is  prepared  by  digesting  a  {q.\n  grams 
of  cochineal  with  a  250-c.c.  mixture  of  one  part  of  alcohol 
and  three  or  four  parts  of  water,  in  the  cold.  After  several 
hours  the  solution  is  filtered  and  it  is  then  ready  for  use.  In 
the  phosphoric  acid  test  a  few  drops  of  this  tincture  are 
added  to  the  urine,  or  phosphate  solution,  in  the  evaporat- 
ing dish  ;  the  heat  is  then  applied,  and  the  standard  uranium 
solution  added  until  a  faint  but  distinct  permanent  green 
color  appears.  The  green  color  begins  to  appear  as  soon 
as  there  is  the  slightest  excess  of  uranium  in  the  solution — 
in  other  words,  as  soon  as  the  phosphoric  acid  has  been 
entirely  precipitated. 

Quantitative  Estimation  of  Phosphoric  Acid  Com- 
bined with  Calcium  and  Magnesium  (Earthy  Phos- 
phates).— Process. — Take  200  c.c.  of  urine,  precipitate 
with  ammonic  hydrate  with  the  aid  of  gentle  heat,  allow 
to  stand  from  twelve  to  twenty-four  hours,  then  filter  and 
wash  with  ammonia  water.  The  filter-paper  is  then  pierced 
at  the  point  and  the  precipitate  washed  through  into  a 
beaker  with  a  stream  of  hot  water,  and  dissolved  while  warm 
in  as  little  acetic  acid  as  possible.  Add  5  c.c.  of  the 
sodium  acetate  solution,  dilute  to  50  c.c,  and  proceed  as 
previously  indicated.  The  difference  between  the  total 
amount  of  phosphoric  acid  and  that  in  combination  with 


SULPHATES.  Ill 

calcium  and  magnesium — earthy  phosphates — also  repre- 
sents the  quantity  combined  with  the  alkalies — alkaline 
phosphates. 

Purdy's  Centrifugal  Method  for  Total  Phosphoric 
Acid. — Fill  the  percentage  tubes  to  the  lo-c.c.  mark  with 
the  urine  to  be  tested,  and  add  magnesia  mixture  (formula, 
see  p.  1 08)  to  the  15-c.c.  mark.  The  tubes  are  then  closed 
and  inverted  several  times,  until  the  urine  and  reagent  are 
thoroughly  mixed.  The  tubes  are  next  placed  in  the  cen- 
trifuge and  revolved  for  three  successive  periods  of  five 
minutes  each  at  the  rate  of  looo  revolutions  a  minute. 
The  volume  percentage  is  then  read  off  In  normal  urine 
this  will  be  found  to  be  in  the  neighborhood  of  8  per  cent. 

The  author  has  obtained,  from  a  large  number  of  obser- 
vations, a  standard  of  percentage  by  weight,  by  a  com- 
parison of  the  volume  percentages  with  the  volumetric 
determinations.  He  has  found  that  each  -j^  of  a  c.c.  of 
precipitate  calculated  as  PjO.  is  equivalent  to  0.0225  per 
cent,  by  weight. 

SULPHATES. 

Sulphuric  acid  is  present  in  the  urine  in  two  forms — as 
ordinary  alkaline  sulphates  of  potassium  and  sodium  (pre- 
formed sulphuric  acid),  and  as  ethereal  sulphates  ^  (conjugate 
sulphuric  acid).  The  sulphates  are  derived  partly  from  the 
food  and  partly  from  the  chemic  changes  of  proteids  in  the 
tissues.  The  albuminous  substances  taken  as  food  contain 
sulphur,  which  becomes  oxidized  in  the  economy  and  re- 
sults in  sulphuric  acid,  some  of  which,  in  turn,  immediately 
combines  with  a  portion  of  the  sodium  and  potassium  to 
forrn  ordinary  sulphates,  and  a  small  portion  to  form  the 
ethereal  sulphates  by  pairing. 

The  total  quantity  of  sulphuric  acid  in  the  twenty-four- 
hour  amount  of  urine  of  an  adult  taking  a  mixed  diet  is 
from  1.5  to  3  grams,  or  an  average  of  2  grams.  About 
one-tenth  of  the  total  sulphuric  acid  is  in  the  form  of  ethe- 
real sulphates.  The  quantity  of  sulphuric  acid  is  subject 
to  considerable  variation,  being  largely  dependent  upon  the 
amount  of  proteid  food  ingested. 

The  sulphates  are  never  found  in  the  urine  as  a  deposit, 
owing  to  the  fact  that  they  are  very  soluble  compounds. 

1  See  p.  83. 


112        INORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

Clinical  Significance. — The  sulphates  are  increased  in 
acute  fevers,  probably  due  to  the  markedly  increased  met- 
abolism. According  to  Bence  Jones,  they  are  especially 
increased  in  acute  inflammatory  diseases  of  the  brain  and 
spinal  cord  and  in  delirium. 

The  sulphates  are  diminished  in  all  diseases,  especially 
the  chronic  forms,  and  during  the  convalescent  stage  of 
acute  diseases,  when  the  metabolism  and  appetite  are  much 
diminished.  They  are  notably  diminished  in  cases  of  car- 
bolic acid  poisoning,  or  following  the  internal  or  external 
use  of  large  amounts  of  any  phenol  compound,  such  as 
salol,  lysol,  etc  ;  under  such  circumstances,  however,  the 
diminution  of  the  ordinary  sulphates  is  attended  with  a 
corresponding  increase  of  the  ethereal  sulphates  (phenol- 
potassium  sulphate). 

In  general,  it  may  be  stated  that  the  variation  in  the 
quantity  of  ordinary  sulphates  eliminated  in  the  urine  runs 
parallel  to  that  of  urea. 

Detection. — The  following  test  serves  for  both  the  de- 
tection and  approximate  estimation  :  Take  one-half  test-tube 
of  filtered  urine  and  add  from  one  to  two  fingerbreadths 
of  barium  solution.  ^  A  white  precipitate  occurs  which,  if  it 
fills  one-half  the  concavity  of  the  test-tube  in  from  eighteen 
to  twenty -four  hours,  may  be  considered  normal  in  quantity  ; 
if  less  than  one-half  the  concavity,  diminished  ;  and  if  more 
than  one-half  the  concavity,  increased. 

Quantitative  Determination. — i.  Total  Sulphuric 
Acid. — For  the  determination  of  the  total  amount  of  sul- 
phuric acid  (SO3) — /.  e.,  preformed  and  conjugate  sulphuric 
acid  together — one  of  two  methods  is  adopted  :  {a)  Gravi- 
metric method  and  {h)  volumetric  method. 

{a)  Gravimetric MctJiod. — This  method  consists  in  weighing 
the  precipitate  of  barium  sulphate  obtained  by  adding  barium 
chloride  to  a  known  volume  of  urine  ;  100  parts  of  sulphate 
of  barium  correspond  to  34.33  parts  of  sulphuric  acid  (SO3). 

Method  [Sa/koivski). — Take  100  c.c.  of  urine  in  a  beaker, 
and  acidulate  with  5  c.c.  of  pure  hydrochloric  acid.  This 
mixture  is  then  boiled,  and  chloride  of  barium  added  to  the 
boiling  fluid  until  no  more  precipitate  occurs. 

The  precipitate  is  collected  on  a  small  filter  of  known 
ash,   and  washed  with   hot   distilled   water   until    no   more 

1  Barmm  Solution — Barium  chloride,  4  parts  ;  concentrated  hydrochloric 
acid,  I  part ;  distilled  water,  16  parts. 


SULPHATES.  113 

barium  chloride  occurs  in  the  filtrate  :  /.  c,  until  the  filtrate 
remains  clear  after  the  addition  of  a  few  drops  of  sul- 
phuric acid.  Then  wash  with  hot  alcohol  and  afterward 
with  ether.  Remove  the  filter,  and  place  it  with  its  contents 
in  a  platinum  crucible.  Heat  to  redness.  Cool  over  sul- 
phuric acid  in  an  exsiccator  ;  w^eigh,  and  deduct  the  weight 
of  the  crucible  and  filter  ash.  The  remainder  is  the  weight 
of  barium  sulphate  formed,  from  which  the  SO3  is  calcu- 
lated— 100  parts  of  barium  sulphate  corresponding  to  34.33 
parts  of  SO3. 

Correction. — When  the  experiment  is  carried  out  as  above, 
there  is  a  slight  error  from  the  formation  of  a  small  quan- 
tity of  sulphide  of  barium.  This  may  be  corrected  as  fol- 
lows :  After  the  platinum  crucible  has  cooled,  add  a  few 
drops  of  pure  sulphuric  acid,  which  converts  into  a  sulphate 
any  sulphide  present.  The  contents  of  the  crucible  are 
again  heated  to  redness  to  drive  off  any  excess  of  sulphuric 
acid,  cooled  and  dried  over  sulphuric  acid,  and  weighed. 

{b)  Volumetric  Method. — This  process  is  conducted  by 
adding  a  standard  solution  of  barium  chloride  to  a  given 
quantity  of  urine  as  long  as  a  precipitate  occurs. 

The  following  solutions  are  necessary  : 

1.  A  standard  solution  of  barium  chloride  made  by  dis- 
solving 30.54  grams  of  pure  crystallized  barium  chloride  in 
water,  and  diluting  to  exactly  one  liter  ;  i  cubic  centimeter 
corresponds  to  0.0 10  gram  of  SO3. 

2.  An  aqueous  solution  of  potassium  sulphate  so  made 
that  one  liter  will  contain  21.775  grams  of  the  salt. 

Process. — Place  50  c.c.  of  the  urine  in  a  flask  or  small 
beaker,  and  add  from  5  to  10  c.c.  of  pure  hydrochloric 
acid.  The  mixture  is  then  boiled  over  a  free  flame  for  fif- 
teen minutes,  or  heated  on  a  water-bath  for  one  hour.  To 
the  hot  fluid  the  standard  barium  chloride  solution  is  added, 
I  c.c.  at  a  time,  until  a  precipitate  fails  to  occur.  After  5 
to  8  c.c.  of  the  standard  solution  have  been  added,  filter  a 
small  portion  of  the  mixture  through  a  very  small  filter- 
paper,  and  to  the  filtrate  add  a  few^  drops  of  the  standard 
solution.  If  a  precipitate  occurs,  return  the  whole  to  the 
flask,  add  more  barium  solution,  and  test  as  before.  Con- 
tinue until  no  more  precipitate  is  formed  on  the  addition  of 
the  barium  chloride  solution.  Any  excess  of  barium  (that 
uncombined  with  sulphuric  acid)  is  show^n  by  placing  a  drop 
or  two  of  the  filtrate  on  a  glass  plate  over  a  dark  back- 
8 


114        INORGANIC  CONSTITUENTS  OF  NORMAL  URINIi 

ground,  and  adding  a  drop  or  two  of  the  solution  of  potas- 
sium sulphate,  when  a  decided  cloudiness  appears.  This 
excess  of  barium  must  be  avoided,  and,  therefore,  in  the 
test  with  potassium  sulphate  only  the  slightest  cloudiness 
should  appear,  which  shows  that  just  the  right  amount  of 
barium  has  been  added  ;  if  an  excess  of  barium  is  present, 
the  entire  analysis  must  be  repeated. 

The  quantity  of  sulphuric  acid  is  calculated  from  the 
amount  of  barium  chloride  solution  used — one  cubic  centi- 
meter of  which  corresponds  to  o.oio  gram  of  SO3. 

2.  Conjugate  Sulphuric  Acid  (Ethereal  Sulphates). — 
Salkinvski's  Method. — One  hundred  cubic  centimeters  of 
clear,  filtered  urine  are  mixed  with  100  c.c.  of  an  alkaline 
solution  of  barium  chloride  (saturated  solution  of  barium 
chloride,  i  part ;  and  a  saturated  solution  of  barium  hydrate, 
2  parts,  both  saturated  in  the  cold),  the  mixture  being 
thoroughly  stirred.  After  a  few  minutes  this  is  filtered 
through  a  dry  filter  into  a  dry  graduate  up  to  the  loo-c.c. 
mark.  This  portion,  corresponding  to  50  c.c.  of  urine,  is 
now  strongly  acidulated  with  10  c.c.  of  hydrochloric  acid, 
boiled,  kept  at  100°  C.  on  the  water-bath  for  an  hour,  and 
then  allowed  to  stand  until  the  precipitate  has  completely 
settled  :  if  possible,  it  should  remain  undisturbed  for  twenty- 
four  hours.  The  further  treatment  of  this  precipitate  (con- 
jugate sulphates)  is  then  carried  out  as  in  the  above- 
described  gravimetric  process.     (See  (rt).) 

Calculations. — The  molecular  weight  of  BaSO^  being 
232.82  ;  that  of  SO3,  79.86  ;  of  HgSO^,  97.82  ;  and  of  S, 
32,  the  figure  expressing  the  amount  of  H2SO^,  SO3,  or  S, 
corresponding  to  i  gram  of  BaSO^,  is  found  according  to 
the  following  equations  : 

232.82  :  79.86  :  :  I  :  .\ ,  and  .r  =  0.34301.     .  ■.     I  gram  of  BaSO^  =  O.3430I 

gram  of  SO.,. 
232.82  :  97.82  :  :  I  :  x,  and  jr  =  0.42015.     .  •.     I  gram  of  BaSO^  =  O.42015 

gram  of  H.^SO^. 
232.82  :  32  :  :  I  :  x,  and  x    -0. 13744.      .".       I    gram  of  BaSO^  ;=  0. 1 3744 

gram  of  S. 

To  calculate  results,  it  is  only  necessary  to  multiply  the 
weight  of  BaSO^  found  by  0.34301,  0.42015,  or  0.13744, 
in  order  to  ascertain  the  amount  of  sulphuric  acid  contained 
in  50  c.c.  of  urine  in  terms  of  SO,,  H^SO^,  or  S,  respectively. 
This  method  of  calculation  applies  to  the  gravimetric  esti- 


CARBONATES.  115 

mation  of  both  the  total  sulphates  and  the  combined  sul- 
phates. 

To  obtain  the  amount  of  preformed  sulphuric  acid,  or 
that  in  combination  with  the  alkalies,  subtract  the  amount 
of  combined  SO.,  from  the  total  amount  of  SO3.  The  dif- 
ference is  the  preformed  SO3. 

Example  :  One  hundred  cubic  centimeters  of  urine  gave 
0.5  gram  of  total  barium  sulphate.  Then  0.5  multiplied  by 
0.34301  =0.171  gram  of  total  SO.^.  Another  100  c.c.  of 
the  same  urine  gave  0.05  gram  of  barium  sulphate  from  the 
ethereal  sulphates  ;  then  0.05  multiplied  by  0.34301  = 
0.017  gram  of  combined  SO3.  The  difference  between  the 
total  and  the  combined  803  =  0.171  — 0.017  =  0.154 
gram  of  SO3  in  combination  with  the  alkalies. 


CARBONATES. 

A  freshly  passed  urine  of  alkaline  reaction  generally  con- 
tains small  quantities  of  carbonates  and  bicarbonates  of 
sodium,  magnesium,  calcium,  and  ammonium,  all  of  which 
arise  in  the  economy  from  the  carbonates  of  the  food,  or 
from  salts  of  malic,  tartaric,  lactic,  succinic,  and  other  vegeta- 
ble acids  ingested  with  the  food.  They  are,  therefore,  most 
abundant  in  the  urine  of  herbivora,  whose  urine  is  thus 
rendered  alkaline.  A  urine  containing  carbonates  is  either 
turbid  when  passed,  or  soon  becomes  so  on  standing.  The 
deposit,  if  allowed  to  settle,  will,  on  examination,  be  found 
to  consist  of  calcium  carbonate  mixed  with  phosphates. 

According  to  Wurster  and  Schmidt,^  a  liter  of  normal 
human  urine  of  a  specific  gravity  of  1020,  if  acid  in  reac- 
tion, contains,  on  an  average,  from  40  to  50  c.c,  and  if 
neutral  or  alkaline,  over  100  c.c.  of  carbonic  acid,  which  is 
capable  of  being  expelled  by  a  current  of  air.  The  amount 
of  carbonic  acid  per  100  c.c.  varies  between  17  c.c.  (urine 
of  low  specific  gravity)  and  294  c.c.  (urine  of  high  specific 
gravity). 

Carbonic  acid  forms  neutral  (normal)  and  acid  salts.  Of 
the  alkaline  carbonates,  both  the  acid  and  the  normal  are 
soluble,  but  the  acid  is  considerably  less  soluble  than  the 
normal.  The  normal  carbonates  of  calcium  and  magnesium, 
on  the  other  hand,  are  ver\'  slightly  soluble,  but  the  acid  is 

'  "Centralbl.  f.  Physiologie,"   1887,  421. 


116        INORGANIC  CONSTITUENTS  OF  NORMAL  URINE. 

more  soluble  than  the  normal.     The  carbonate  of  ammo- 
nium is  volatile  at  ordinary  temperature. 

For  the  detection  and  quantitative  determination  of  car- 
bonic acid,  both  free  and  combined,  see  Neubauer  and 
Vogel,  "Analyse  des  Harns,"  Bd.  i,  1898,  S.  37  u.  735. 


IRON. 

Iron  is  found  only  in  minute  traces  in  the  residue  of  the 
urine  after  ignition.  According  to  Magnier,  the  amount  of 
iron  in  a  healthy  man  of  medium  weight  varies  between  0.003 
and  0.0 1 1  gram  in  a  liter.  The  coloring-matter,  which  is 
precipitated  with  the  uric  acid  on  the  addition  of  concen- 
trated hydrochloric  acid,  according  to  Kunkel,  contains 
iron. 

Detection. — The  ash  of  the  residue  of  urine  is  always 
used  for  the  isolation  and  detection  of  iron.  It  is  dissolved 
in  a  little  hydrochloric  acid,  and  the  solution  divided  into 
two  parts.  The  first  part  is  boiled  with  a  drop  of  nitric 
acid  and  treated  with  a  solution  of  potassium  sulphocyanide 
which,  if  ferric  oxide  be  present,  produces  a  red  or  blood- 
red  color.  If  potassium  ferrocyanide  is  added  to  the  other 
half  of  the  solution,  after  boiling  with  nitric  acid  and  dilut- 
ing, flocculi  of  Prussian  blue  separate  after  standing  a  time. 

For  the  quantitative  determination  of  iron  and  further 
information  regarding  this  substance  the  reader  is  referred 
to  Neubauer  and  Vogel,  "  Analyse  des  Harns,"  Bd.  i, 
1898,  S.  47  u.  750. 

HYDROGEN  PEROXIDE. 

This  substance  was  first  detected  in  the  urine  by  Schonbein.  ^ 
The  most  reliable  reaction  that  serves  for  its  recognition  depends 
upon  the  power  it  possesses  of  bleaching  a  dilute  tincture  of 
indigo.     The  urine  to  be  tested  must  be  perfectly  fresh. 

The  relative  unimportance  of  this  substance  in  the  urine  for- 
bids more  than  a  mere  mention  here.  ^ 

1  "  Joum.  f.  prakt.  Ch.,"   xcii.   i68,   1864. 

2  See  Neubauer  and  Vogel,  "  Analyse  des  Harns,"  1898,  S.  39. 


CHAPTER  IV. 

ABNORMAL  CONSTITUENTS  OF  URINK 

PROTEIDS. 

Under  pathologic  conditions  urine  may  contain  a  number 
of  proteids — /.  r.,  serum  albumin,  serum  (or  para-)  globulin, 
albumose,  peptone,  hemoglobin  and  methemoglobin,  and 
fibrin  and  fibrinogen.  Egg-albumin  is  occasionally  found, 
especially  after  the  liberal  ingestion  of  eggs  as  a  food. 
Several  of  these  proteids  may  be  present  iii  the  urine  at  the 
same  time,  or,  on  the  other  hand,  only  a  limited  number 
present,  such  as  albumin  and  globulin,  albumin  and  hemo- 
globin, etc. 

General  Reactions  of  the  Proteids. 
A.     Color  tests. 

1.  Xanthoproteic  Reaction. — Heat  the  solution  of  the 
proteid  with  concentrated  nitric  acid.  There  results  a  yellow 
color,  which,  on  the  addition  of  an  alkaline  hydrate,  changes 
to  a  deep  orange.  If  ftiuch  proteid,  except  albumose  and  pep- 
tone, be  present,  a  yellow  precipitate  is  obtained  at  the  same 
time;  with  less  proteid,  its  solution  merely  turns  yellow  on 
boiling,  and  orange  on  the  addition  of  an  alkali  ;  if  only  a  trace 
is  present,  no  yellow  color  is  observed  until  after  the  addition 
of  the  alkali. 

2.  Millon's  Reaction. — With  Millon's  reagent  ^  proteids, 
when  present  in  sufficient  quantity,  give  a  precipitate  that  turns 
red  on  heating.  If  only  present  in  traces,  no  precipitate  is  ob- 
served on  heating,  but  merely  a  red  colorization  of  the  solution. 

3.  Piotrowski's  Reaction. — If  a  solution  of  the  proteid  be 
mixed  with  an  excess  of  a  concentrated  solution  of  sodic  hy- 
drate, and  one  or  two  drops  of  a  dilute  solution  of  sulphate  of 
copper  be  added,  a  violet  color  is  obtained,  which  deepens  on 
boiling.  Albumoses  and  peptones  give  a  rose-red  color  {Jniiret 
reaction)  ;  care  must  be  taken  in  the  addition  of  the  cupric 
sulphate  solution,  since  an  excess  gives  a  reddish-violet  color 

^  See  foot-note,  p.  168. 
117 


118  ABNORMAL  CONSTITUENTS  OF  URINE. 

somewhat  similar  to  that  obtained  in  the  presence  of  other  pro- 
teids. 

The  foregoing  tests  serve  to  detect  the  smallest  traces  of  pro- 
teids. 

B.  General  Precipitants. — Solutions  of  proteids  are  pre- 
cipitated by  the  following  reagents  (peptones  are  exceptions 
in  most  cases)  : 

1.  Render  the  solution  strongly  acid  with  acetic  acid,  and 
add  a  few  drops  of  a  solution  of  potassium  ferrocyanide.  A 
precipitate  shows  the  presence  of  proteids,  except  true  peptone 
and  some  forms  of  albumose. 

2.  Render  the  fluid  as  before  strongly  acid  with  acetic  acid, 
add  an  equal  volume  of  concentrated  solution  of  sodium  sul- 
phate, and  boil.  A  precipitate  forms  if  proteids,  except  pep- 
tone, are  present.  This  test  is  particularly  useful,  since  the 
reagents  used  do  not  produce  any  decomposition  of  other 
substances  that  may  be  present,  and  do  not  interfere  with  cer- 
tain other  tests  that  may  be  applied  after  the  removal  of  the 
proteids  by  filtration. 

3.  Completely  saturate  the  fluid  with  ammonium  sulphate, 
having  previously  neutralized  and  then  rendered /i?/////)' acid  with 
acetic  acid  ;  this  precipitates  all  proteids  except  peptones. 

4.  Alcohol,  tannic  acid,  phosphotungstic  acid,  and  potassio- 
mercuric  iodide  are  also  general  precipitants,  the  last  two  being 
particularly  useful  for  delicate  tests. 

The  term  "  albumin,"  in  its  ordinary  clinical  use,  includes 
not  only  serum  albumin,  but  also  serum  globulin,  and,  in 
rare  instances,  albumose.  It  should  be  remembered  that 
these  proteids  differ  in  many  respects,  and,  so  far  as  is  pos- 
sible, should  be  separately  identified. 


ALBUMIN. 

Serum  albumin  is  doubtless  the  most  important  proteid 
found  in  the  urine.  It  can  safely  be  considered  an  abnor- 
mal constituent  when  present  in  amounts  capable  of  being 
detected  by  the  tests  that  are  ordinarily  used.  Whether 
or  not  albumin  is  present  in  minute  traces  in  the  urine  in 
health — such  traces  being  incapable  of  detection  by  the 
tests  generally  employed — is  still  a  debated  question.  From 
a  practical  point  of  view  this  question  can  be  disregarded. 

Albuminuria  is  not  necessarily  an  indication  of  renal  dis- 
ease, for  albumin  may  be  present  in  the  urine  without  the 
slightest  alteration  in  the  renal  structure.  In  general,  the 
presence   of  albumin  indicates  a  disturbance  or  disease  in 


ALBUMIN.  119 

some  part  of  the  genito-urinar}'  tract,  and  with  one  exception 
— /.  c,  "  functional  albuminuria" — is  always  accompanied 
by  formed  physiologic  or  pathologic  elements  in  the  urinary 
sediment. 

Albumin  is  not  capable  of  ciystallization  ;  it  is  soluble  in 
water,  in  dilute  saline  solutions,  and  in  saturated  solutions 
of  sodium  chloride  and  magnesium  sulphate.  It  is,  how- 
ever, precipitated  by  saturating  with  sodium  or  ammonium 
sulphate.  It  is  coagulated  by  heat,  usually  at  from  70°  to 
73°  C,  particularly  in  the  presence  of  sodium  chloride.  It 
is  not  precipitated  by  ether,  in  which  respect  it  differs  from 
egg-albumin.  Under  ordinary  conditions  it  does  not  pass 
through  animal  membranes. 

Causes  of  Albuminuria. — In  general,  the  causes  of 
albumin  in  the  urine  are:  (i)  Changes  in  the  kidney  structure, 
which,  on  account  of  its  abnormal  state,  allows  the  albumin 
to  transude  ;  (2)  alterations  in  the  blood  pressure  in  the 
kidneys ;  (3)  abnormal  changes  in  the  quality  of  the 
blood  entering  the  kidney,  thus  rendering  its  serum  albu- 
min more  diffusible  ;  and  (4)  disturbances  or  diseases  of 
the  urinary  tract  below  the  kidneys — /.  e.,  renal  pelvis, 
ureters,  bladder,  prostate  gland,  and  urethra.  Under  this 
heading  may  be  included,  also,  albuminous  elements  enter- 
ing from  the  genital  tract. 

Clinical  Importance. —  i.  Albuminuria  due  to  patho- 
logic changes — inflammatory  and  degenerative — in  the 
kidneys  is  without  doubt  the  most  important,  and  often  the 
most  serious,  form.  These  changes  include  the  variety  of 
diseases  commonly  grouped  under  the  term  of  Bright' s 
disease.  Not  only  do  we  have  to  deal  with  these  extensive 
diseases  of  the  kidney,  but  also  with  certain  disturbances 
of  the  renal  function  that  are  accompanied  by  the  pres- 
ence of  albumin. 

The  quantity  of  albumin  in  the  urine  in  various  renal  af- 
fections may  vary  between  the  slightest  possible  trace  and 
from  three  to  four  per  cent.  From  the  quantity  of  albumin 
alone  it  is  impossible  to  judge  in  all  cases  of  the  nature  or 
severity  of  the  renal  changes.  For  instance,  the  grave  con- 
dition— chronic  interstitial  nephritis — may  exist  with  only 
the  slightest  possible  trace  of  albumin  in  the  urine.  On  the 
other  hand,  a  simple  renal  congestion  may,  for  a  short 
time,  be  accompanied  by  from  y^  to  y^  of  one  per  cent,  of 
albumin.     In    certain  conditions — for   example,    an    acute 


120  ABNORMAL  CONSTITUENTS  OF  URINE. 

nephritis  in  which  the  diagnosis  has  already  been  estab- 
Hshed — very  general  information  concerning  the  progress 
of  the  disease  may  be  gained  by  examining  the  urine  daily 
for  albumin.  Such  information,  however,  is  unsafe  if  not 
accompanied  by  a  complete  chemic  and  microscopic  exam- 
ination of  the  twenty-foiu'-hour  secretion. 

2.  The  second  form — alterations  in  the  blood  pressure 
in  the  kidneys — is  a  common  cause  of  albuminuria.  It  is 
always  the  result  of  circulatory  disturbances  that  include 
the  renal  vessels.  There  is  usually  more  or  less  structural 
change  in  the  kidneys,  and,  besides  albuminuria,  a  greater 
or  smaller  number  of  formed  pathologic  elements  in  the 
sediment.  There  may  be  an  increase  in  the  arterial  pres- 
sure, as  in  certain  affections  of  the  nervous  system  in  which 
there  is  an  interference  with  the  vasomotor  regulation  of  the 
coats  of  the  blood-vessels  ;  also  in  sudden  exposure  to  cold 
and  zvct,  in  which  case  the  internal  organs  become  ab- 
normally filled  with  blood ;  and  in  arteriosclerosis.  On 
the  other  hand,  the  blood  pressure  may  be  diminished,  as 
in  certain  forms  of  cardiac  disease,  which  results  in  a  back 
pressure  in  the  renal  veins  (passive  cogestion),  and  hence 
albuminuria.  The  pressure  of  tumors  or  of  the  pregnant 
uterus  on  the  abdominal  veins  will  often  cause  albuminuria, 
but  soon  after  the  cause  is  removed  the  albumin  disappears 
from  the  urine. 

So-called"  Functional  or  Physiologic  Albuminuria." 
— The  most  marked  condition  in  which  this  occurs  is  after 
prolonged  muscular  exertion.  A  study  of  this  condition 
was  made  by  Leube,i  who  found  albumin  in  the  urine  in  i6 
per  cent,  of  soldiers  after  a  prolonged  march;  Oertels^  found 
it  in  3  per  cent,  of  the  cases  examined. 

3.  This  form,  which  causes  albuminuria  by  changes  in 
the  quality  of  the  blood  entering  the  kidney,  is  notably 
seen  in  cases  of  anemia  (this  is  perhaps  partially  explained  by 
the  lessened  nutrition  of  the  renal  cells),  and  in  the  first  stage 
of  the  convalescence  from  cholera.  In  phosphorus-poison- 
ing and  hemoglobinemia,  also  in  carbon  monoxide  poison- 
ing and  after  the  excessive  use  of  morphine,  the  blood 
is  probably  so  altered  as  to  permit  the  transudation  of  the 
serum  albumin  into  the   renal   tubules.      In   some  of  these 

1  *' Virchow's  archiv,"  Lxxii,  145  ;  i.xxix. 

2  "  Ziemssen's  Handbucli  der  allgcmein.  Therapie,"  IV. 


ALBUMIN.  121 

cases  of  poisoning  the  kidneys  are  simultaneously  affected, 
so  that  the  cause  of  the  albuminuria  may  be  partly  ex- 
plained by  the  renal  disturbance. 

4.  This  form  of  albuminuria  has  been  variously  termed 
false,  adventitious,  or  cxceidoital.  Under  this  class  are  in- 
cluded a  large  number  of  urines  that  contain  comparatively 
small  amounts  of  albumin.  The  quantity  of  albumin  usually 
depends  upon  the  amount  of  blood  and  pus  coming  from 
the  diseased  area,  and,  therefore,  may  be  abundant  if  much 
blood  is  present.  In  many  instances,  particularly  when  the 
disturbance  or  disease  is  located  in  the  bladder  or  urethra, 
the  kidney  is  not  affected  at  all  by  the  condition,  the  urine 
being  normal  until  it  reaches  the  affected  area.  On  the 
other  hand,  in  cases  of  pyelitis  and  prostatitis,  the  function 
of  the  kidneys  is  very  apt  to  be  secondarily  disturbed  by 
the  local  disease,  and  consequently  more  or  less  albumin 
of  renal  origin.  Albumin  not  infrequently  gets  into  the 
urine  from  the  genital  tract :  in  the  female,  from  the  vagi- 
nal discharge,  consisting  of  a  mixture  of  more  or  less  pus, 
blood,  and  epithelium,  also,  occasionally,  menstrual  fluid  ; 
in  the  male,  from  seminal  fluid.  As  a  rule,  the  source  of 
albumin  in  such  cases  may  be  determined  by  both  chemic 
and  microscopic  investigation,  together  with  the  local  symp- 
toms. It  is  important  that  this  variety  of  albuminuria  be 
borne  in  mind  by  the  student  in  order  to  avoid  error. 

Albuminuria  of  Adolescence  and  Cyclic  Albumin- 
uria.— These  forms  may,  or  may  not,  be  accompanied 
by  a  renal  disturbance  :  in  other  words,  renal  casts  and 
cells  may  or  may  not  be  present  in  the  sediment.  A 
large  proportion  of  these  cases  occurs  in  youths  and  young 
adults.  The  quantity  of  albumin  usually  varies  between  a 
slightest  possible  trace  and  one -half  of  one  per  cent.,  gener- 
ally averaging  one-eighth  of  one  per  cent.,  or  less.  The 
quantity  often  varies  as  the  time  of  day — /.  c.,  being  less  (or 
sometimes  absent)  at  night  during  the  hours  of  rest,  appear- 
ing in  the  morning,  especially  upon  exercising,  increasing 
during  the  day,  and  diminishing  toward  evening.  In  some 
of  these  cases  the  amount  of  albumin  is  fairly  constant,  day 
and  night,  particularly  in  cases  of  albuminuria  of  adoles- 
cence. The  presence  of  albumin  may  continue  for  weeks, 
months,  or  even  years,  and  then  finally  disappear.  Little 
can  be  said  concerning  the  causes  of  these  forms  of  albu- 
minuria.    There  are  often  circulatory  changes  that  appear 


122 


ABNORMAL  CONSTITUENTS  OF  URINE. 


to  be  functional  in  character,  and  the  individual  is  generally 
found  to  be  somewhat  below  the  standard  of  vigorous 
health.  An  abnormal  increase  in  the  blood  pressure  or 
changes  in  the  quality  of  the  blood  have  been  suggested  as 
the  possible  explanation  of  this  form  of  albuminuria. 

It  is  safe  to  conclude  from  the  foregoing  consideration 
that  the  presence  of  albumin  in  the  urine  is  to  be  regarded 
merely  as  a  "  danger  signal,"  and  that  when  it  is  present,  a 
further  chemic  and  microscopic  study  of  the  urine  is  neces- 
sary before  deciding  as  to  the  existing  condition.  Albu- 
minuria in  itself  can  not  be  considered  diagnostic. 

Detection  of  Albumin  in  Urine. — Nitric  Acid  Test. 
— Alzvays  filter  the  urine  to  be  tested.  This  is  an  important 
step,  even  though  the  urine  appears 
to  be  perfectly  clear,  since  all  urines 
contain  a  certain  amount  of  sus- 
pended matter,  which  must  be  re- 
moved in  order  to  detect  the  smallest 
traces  of  albumin. 

Take  a  perfectly  clear  and  dry  wine- 
glass (Fig.  13),!  and  one-half  fill  with 
the  filtered  urine.  Incline  the  glass 
so  that  the  urine  reaches  nearly  the 
edge,  and  then  underlie  zvitJi  concen- 
trated nitric  acid  (C.  P.),  pouring  it 
from  the  bottle  as  slozvly  as  possible 
(Fig.  14),  until  the  acid  equals  ap- 
proximately onc-thij'd  the  volume  of 
urine  used.  If  albumin  be  present,  a 
more  or  less  distinct  white  band  or 
zone  of  coagulated  albumin  will  be 
seen  just  abov^e  the  junction  of  the 
acid  and  urine.  This  zone  will  var>'  in  thickness  according 
to  the  quantity  of  albumin  present,  the  rapidity  with  which 
the  acid  is  poured,  or,  in  other  words,  the  extent  to  which 
the  acid  and  urine  are  mixed,  and,  lastly,  the  amount  of 
effervescence  that  follows  the  addition  of  acid  (decomposi- 
tion of  carbonate,  and  in  case  yellow  nitric  acid  is  used,  the 
decomposition  of  the  urea  and  uric  acid,  with  effervescence). 


Fig.  13. — Wine-glass   (one- 
half  actual  size). 


1  The  wine-glass  here  represented  is  perhaps  best  suited  for  the  satisfactory 
performance  of  the  nitric  acid  test.  It  is  made  of  clear  white  glass,  and  is 
free  from  defects.  It  was  formerly  manufactured  by  the  Sandwich  Glass  Co,, 
under  the  name  of  "  CoUamore  Wine  Glass." 


ALBUMIN. 


123 


Approximate  Estimation  of  Albumin. — If  in  every  case 
the  proportion  of  urine  and  acid  is  as  previously  indicated, 
and  the  nitric  acid  is  poured  from  the  bottle  as  slowly  as 
possible,  much  can  be  told  concerning  the  approximate 
quantity  of  albumin  present  by  the  appearance  of  the  zone 
obtained.  It  is  very  difficult,  and,  indeed,  practically  impos- 
sible, to  give  the  percentage  of  albumin  as  judged  from  the 
zone,  if  the  quantity  is  less  than  a  trace ;  if  more  than  a 
trace,  a  general  idea  as  to  the  percentage  can  be  given. 

{li)  Slightest  Possible  Trace. — This  is,  naturally,  the 
smallest  amount  of  albumin  capable  of  being  detected  by 
ordinary  tests,  and  can  certainly  be  considered  an  entity  in 
connection  with  the  nitric  acid  test.  These  slightest  traces, 
I  regret  to  say,  are  often  overlooked,  especially  by  the 
inexperienced,  because  the  proper  means  for  their  detection 


Fig.  14. — Method  of  performing  the  nitric  acid  test  for  albumin. 


are  not  employed.  It  is  important,  first  of  all,  that  the 
wine-glass  be  perfectly  clean,  and,  secondly,  that  a  dark 
background  be  adjusted  obliquely  in  front  of,  or  a  little 
to  one  side  of,  the  glass,  between  the  source  of  light  and 
the  glass,  but  not  so  placed  as  entirely  to  cut  off  the  light. 
(See  Fig.  15.)  In  this  way  the  merest  haze  of  albumin, 
which  is  usually  a  rather  wide,  hazy  band,  approximately 
-jlg  to  "I"  of  an  inch  in  width,  and  not  a  sharp  and  narrow 
band,  is  discernible.  A  clear,  but  usually  narrow,  layer  of 
clear  urine  can  frequently  be  seen  between  this  haze  or 
cloud  of  albumin  and  the  zone  of  acid  urates  that  forms 
higher  up  in  the  layer  of  urine.  The  slightest  possible 
trace  can  not  be  seen  without  the  use  of  a  dark  back- 
ground. 


124 


ABNORMAL  CONSTITUENTS  OF  URINE. 


{b)  Very  Slight  Trace. — This  is  a  faint  zone  which  is  best 
seen  by  using  a  dark  background.  If  the  wine-glass  is 
held  between  the  eye  and  the  light,  a  very  faint  cloud 
may  be  seen,  but  the  observer  will  often  be  in  doubt  as  to 
the  presence  of  albumin  until  a  dark  background  is  used. 
This  zone  can  not  be  discerned  as  the  observer  looks  down 
on  to  the  surface  of  the  urine  :  that  is,  the  bottom  of  the 
wine-glass  can  be  distinctly  seen. 

ic)  Slight  Trace. — This  is  a  distinct  white  zone  which 
can  readily  be  seen  from  the  side  without  a  dark  back- 
ground. In  looking  through  the  urine  from  above  down- 
ward, a  very  faint  cloud  can  be  made  out,  although  the 
bottom  of  the  wine-glass  can  be  distinctly  seen. 


^H 

i 

1 

9 

^ 

rife 

,^ 

£ 

jffB 

fc 

felfemr 

V ■> 

^1 

H^ 

^^ 

fcff 

Fig. 


15. — Method  for  llie  detection  of  minute  quantities  of  albumin.     Lower  zone, 
alljumin  ;  upper  zone,  acid  urates. 


(d)  Trace. — A  trace  of  albumin  is  a  zone  which  is  dis- 
tinctly seen  without  a  dark  background,  when  viewed  from 
the  side.  In  looking  through  the  urine  from  above  down- 
ward a  decided  cloud  is  seen,  but  this  cloud  is  usually  not 
so  dense  as  to  prevent  one's  seeing  the  bottom  of  the 
wine-glass. 

{e)  Large  Trace  (including  -^  of  i  per  cent.). — A  zone 
which,  seen  from  the  side,  is  very  evident,  but  not  granular 
(flocculent).  When  viewed  from'  above  downward,  it  is 
found  to  be  quite  dense,  although  not  so  dense  as  to 
obstruct  entirely  the  transmission  of  a  little  light.     (The 


ALBUMIN.  125 

light  can  be  cut  off  by  placing  the  hand  between  the  source 
of  Hght  and  the  glass.) 

(/)  Onc-ciglitJi  of  One  Per  Cent. — A  marked  zone  which 
is  not  flocculcnt.  The  bottom  of  the  glass  can  not  be 
seen,  although  a  faint  ray  of  light  can  usually  be  seen 
coming  through  the  zone. 

(^)  One-fonrth  of  One  Per  Cent. — A  zone  which  is 
quite  flocculent  when  viewed  from  the  side.  No  light  can 
be  seen  through  the  band  in  looking  from  above  downward. 

{]l)  One-half  of  One  Per  Cent,  or  More. — When  the  quan- 
tity of  albumin  reaches  one-half  of  one  per  cent,  or  more, 
a  dense,  very  floeen lent  h?in6.  forms;  light  can  not  be  seen 
through  it.  Above  one-half  of  one  per  cent,  it  is  difficult 
to  estimate  the  approximate  quantity  present ;  a  quantita- 
tive test  should  then  be  made  according  to  the  instructions 
given  on  page  131. 

If  the  proper  appliances  are  at  hand,  it  is  advisable  to 
make  a  quantitative  determination  of  the  albumin  in  all 
cases  in  which  the  amount  is  a  traee  or  more. 

In  the  nitric  acid  test  practically  nothing  can  be  deter- 
mined from  the  width  of  the  zone  of  albumin.  In  dealing 
with  the  smaller  quantities  the  width  of  the  band  will 
depend  largely  on  the  rapidity  with  which  the  nitric  acid  is 
poured,  and  also  upon  the  amount  of  effervescence  that 
follows  the  addition  of  the  acid.  The  bands  will  usually 
vary  in  width  from  about  ^-^  of  an  inch  to  \  of  an  inch  or 
more.  Usually  in  the  presence  of  the  large  quantities  of 
albumin  the  band  is  quite  narrow,  but  exceedingly  dense. 

Heat  Test. — The  heat  test  for  albumin  depends  upon 
the  separation  (coagulation)  of  this  proteid  from  fluids  which 
are  faintly  acid,  preferably  with  acetic  acid,  by  heating  at  a 
temperature  of  about  75°  C. 

It  is  essential  that  the  urine  should  have  a  faintly  acid 
reaction  ;  for,  if  the  urine  is  alkaline,  the  albumin  is  in  the 
form  of  alkali  albumin,  which  is  not  coagulable  by  heat. 
Again,  if  too  strongly  acidulated,  the  albumin  is  in  the  form 
of  acid  albumin,  which  is  likewise  incapable  of  being  coagu- 
lated by  heat. 

/.  If  the  urine  is  acid,  take  one-half  test-tube  of  the  filtered 
urine,  add  one  drop  (not  more)  of  10  per  cent,  acetic  acid, 
and  mix  thoroughly  ;  hold  the  test-tube  by  the  lower  portion, 
and  boil  the  upper  one-third  of  acidulated  urine.  If  a  cloud 
forms,  it  consists  of  either  albumin  or  earthy  phosphates. 


126  ABNORMAL  CONSTITUENTS  OF  URINE. 

Add  another  drop  or  two  of  acetic  acid,  boil  again,  and  if 
the  cloud  remains,  albumin  is  present ;  if  the  cloud  disap- 
pears, the  precipitate  is  phosphatic. 

2.  If  the  urine  is  alkaline,  take  one-half  test-tube  of  the 
filtered  urine,  add  two  or  three  drops  of  lo  per  cent,  acetic 
acid,  and  boil  the  upper  one-third  of  the  urine  as  directed. 
If  the  urine  has  not  yet  been  rendered  faintly  acid,  a  pre- 
cipitate or  coagulum  of  albumin  will  not  appear  until 
sufficient  acetic  acid  has  been  added,  drop  by  drop,  to 
the  hot  urine,  to  faintly  acidulate.  As  soon  as  the  proper 
reaction  has  been  reached,  a  precipitate  will  appear  if  albu- 
min be  present.  As  stated  previously,  the  further  addition 
of  one  or  two  drops  of  acetic  acid  will  help  to  determine 
whether  the  precipitate  is  phosphatic  or  is  a  coagulum 
of  albumin. 

It  scarcely  ever  happens  that  a  urine,  when  voided,  is 
too  acid  for  the  successful  application  of  the  heat  test,  and 
even  in  a  strongly  acid  urine  it  is  often  necessary  to  use 
one  drop  of  acetic  acid  in  order  that  the  examiner  may  be 
satisfied  of  the  presence  or  absence  of  albumin. 

Nitric  acid,  which  is  often  used  for  acidulation  instead  of 
acetic  acid,  is  liable  to  lead  to  serious  error  in  judging  of 
the  presence  of  albumin  by  the  heat  test.  This  is  espe- 
cially so  if  the  albumin  is  present  in  small  amount,  since 
the  addition  of  so  strong  an  acid  converts  the  albumin  to 
acid  albumin, — syntonin, — which  is  soluble  and  not  coag- 
ulated by  boiling.  Less  danger  exists  in  the  use  of  acetic 
acid  (lo  per  cent.),  providing,  however,  that  an  excess  of  the 
acid  is  avoided.  Nitric  acid  should,  therefore,  not  be  used 
in  connection  with  the  heat  test. 

The  approximate  estimation  of  the  quantity  of  albumin 
from  the  density  of  the  coagulum  of  albumin  by  heat  is  not 
always  a  simple  matter  in  the  hands  of  most  observers, 
since  a  standard  for  comparison  can  not  be  easily  fixed. 
On  the  other  hand,  those  who  prefer  to  use  the  heat  test 
instead  of  the  nitric  acid  test  for  routine  work  can  learn  to 
estimate  the  approximate  quantity  in  a  general  way. 

The  Potassium  Ferrocyanide  and  Acetic  Acid  Test. 
— This  test  may  be  applied  in  two  ways  :  i.  e.,  (a)  by  actual 
mixture  and  {b)  by  the  contact  method. 

{a)  To  a  half  test-tube  of  urine  add  from  three  to  five 
cubic  centimeters  of  a  solution  of  potassium  ferrocyanide 
(i  :  lo),  and  from  one  to  three  cubic  centimeters  of  50  per 


ALBUMIN.  127 

cent,  acetic  acid  ;  the  rea^jents  and  urine  should  be  thor- 
oughly mixed.  If  albumin  be  present,  a  white,  finely  divided 
precipitate  will  appear  within  half  a  minute  or  a  minute. 

(/»)  Take  a  mixture  of  one  part  of  50  per  cent,  acetic  acid 
and  two  parts  of  potassium  ferrocyanide  solution  in  a  wine- 
glass, and  carefully  overlay  with  the  urine  to  be  tested.  If 
albumin  be  present,  a  narrow,  sharply  defined,  white  zone 
will  appear  just  above  the  junction  of  the  two  flluids.  The 
urine  to  be  tested  must  be  acid  in  reaction  in  order  to 
obtain  a  satisfactory  test.  This  reagent  does  not  precipi- 
tate peptones,  alkaloids,  or  phosphates,  but  may  precipitate 
acid  urates.  It  has  been  found  to  react  slightly  with 
artificial  solutions  of  nucleo-albumin. 

A  comparative  experimental  study  of  the  three  tests 
described  convinces  the  writer  of  the  following  order 
of  delicacy  :  (i)  nitric  acid  test;  (2)  heat  test;  (3)  potas- 
sium ferrocyanide  and  acetic  acid  test. 

Other  Tests  for  Albumin. — It  has  long  been  known 
that  albumin  is  coagulated  or  precipitated  by  other  agents 
than  nitric  acid,  heat,  and  potassium  ferrocyanide  and  acetic 
acid.  Some  of  these  tests  have  claimed  much  attention, 
and  have  been  found  to  be  extremely  delicate,  but  it  is  safe 
to  say  that  their  delicacy  is  often  at  the  expense  of  accuracy. 
The  chief  objection  to  many  of  the  tests  is  that  they  pre- 
cipitate other  substances  than  albumin,  and  although  these 
substances  are  distinguished  from  albumin  by  taking  certain 
precautions,  or  by  the  application  of  other  tests,  the  ob- 
server is  either  misled,  and  considers  that  albumin  is  present, 
or  he  is  left  in  a  confused  state  of  mind.  While,  doubtless, 
it  is  desirable  that  we  should  possess  tests  for  albumin 
which  are  very  sensitive,  yet  extreme  delicacy  of  re- 
action is  of  secondary  consideration  and  not  of  clinical 
importance.  Such  tests  should,  therefore,  not  enter  into 
the  routine  examination  of  the  urine,  thus  avoiding  unneces- 
sary confusion. 

Picric  Acid  Test. — This  test  has  been  strongly  advised  by 
Dr.  George  Johnson.  1  The  test  is  applied  as  follows:  Into  a 
test-tube  six  inches  long  pour  a  four-inch  column  of  filtered 
urine.  Then,  holding  the  test-tube  in  a  slanting  position,  pour 
gently  an  inch  of  a  saturated  solution  of  picric  acid  (made  by 
adding  six  or  seven  grains  of  picric  acid  to  a  fluidounce  of  boil- 

*  "Albumin  and  Sugar- testing,"  London,  1884. 


128  ABNORMAL  CONSTITUENTS  OF  URINE. 

ing  distilled  water)  over  the  surface  of  the  urine ;  the  reagent 
thus  mixing  with  only  the  upper  layer  of  the  urine.  As  far  as 
the  yellow  color  of  the  reagent  extends,  the  coagulated  albumin 
renders  the  liquid  turbid,  contrasting  with  the  clear  urine  below. 
In  order  to  obtain  a  satisfactory  reaction  there  must  be  an  actual 
mixture  and  not  a  mere  surface  contact.  When  the  quantity  of 
albumin  is  small  and  the  turbidity  is  slight,  the  application  of 
heat  to  the  upper  part  of  the  turbid  mixture  increases  it.  This 
reagent  also  precipitates  urates,  peptone,  albumose,  vegetable 
alkaloids,  and  mucin,  all  of  which,  except  mucin,  are  dissolved 
by  a  degree  of  heat  much  below  that  of  the  boiling-point. 

The  Potassio-7nercuric-iodide  Test. — This  test  was  sug- 
gested by  M.  Charles  Tanret.  The  reagent  (double  iodide  of 
mercury  and  potassium,  acidulated  with  acetic  acid)  is  prepared 
as  follows:  Bichloride  of  mercury,  1.35  grams;  potassium 
iodide,  3.32  grams;  acetic  acid.  20  c.c.  ;  distilled  water,  suf- 
ficient to  make  100  c.c.  The  bichloride  of  mercury  and  the 
potassium  iodide  should  be  dissolved  separately  in  water,  and 
the  two  solutions  mixed  ;  the  acetic  acid  is  then  added,  and 
the  whole  mixture  made  up  to  100  c.c.  The  contact  method  is 
used,  and  since  the  reagent  is  heavier  than  the  urine,  the  latter 
is  carefully  poured  on  to  the  surface  of  the  reagent  in  a  test- 
tube  or  wine-glass.  If  albumin  be  present,  a  white,  sharply  de- 
fined band  appears  at  the  junction  of  the  two  fluids.  This  test 
precipitates  the  same  substances  as  picric  acid,  including  nucleo- 
albumin.  All  of  these  precipitates  except  albumin  are  dissolved 
by  gentle  heat,  the  precipitate  reappearing  upon  being  cooled. 
According  to  Oliver,  the  precipitate  of  nucleo-albumin  is  not 
dissolved  by  heat  if  a  large  excess  of  reagent  is  used,  the  mer- 
curic salt  apparently  preventing  solution.  This  test  is  exceed- 
ingly delicate. 

Trichloracetic  Acid  Test. — This  test  is  applied  by  means  of 
the  contact  method.  The  reagent  is  prepared  by  dissolving 
15  grams  of  the  crystals  of  trichloracetic  acid  in  about  10  c.c. 
of  distilled  water,  making  a  saturated  solution.  Delicate  results 
are  claimed  for  this  test,  but,  from  the  fact  that  it  precipitates 
mucin  and  nucleo-albumin,  it  can  not  be  regarded  as  a  reliable 
test  for  albumin. 

Sodium  Tungstate. — This  test  was  suggested  by  Dr.  George 
Oliver  as  a  very  sensitive  reagent  for  albumin.  The  reagent  is 
prepared  by  mixing  equal  parts  of  a  saturated  solution  of  sodium 
tungstate  (1:4)  and  a  saturated  solution  of  citric  acid.  The 
contact  method  is  used,  and  since  the  reagent  is  heavier  than 
urine,  it  is  best  applied  by  the  overlaying  method.  The  reagent 
precipitates,  in  addition  to  albumin,  acid  urates,  peptone,  and 
mucin.  It  gives  no  reaction  with  the  alkaloids,  and  all  precipi- 
tates, except  albumin  and  mucin,  are  readily  dissolved  by  heat. 


ALBUMIN.  129 

A  large  number  of  other  so-called  '  *  delicate  tests  ' '  have  been 
suggested  for  the  detection  of  albumin,  only  a  few  of  which  are 
worthy  of  mention:  Acidulated  brine  test  (Roberts),  nitric- 
magnesium  test  (Roberts),  phenic  acid  test  (Millard),  Heiden- 
lang'stest,  Heynsius'stest,  acetic  acid  and  sodium  sulphate,  etc. 

Albumin- test  Papers. — According  to  the  suggestion  of  Dr. 
George  Oliver,  a  number  of  the  tests  named  have  been  prepared 
and  used  in  paper  form.  This  is  accomplished  by  using  chem- 
ically inert  filter-paper,  some  of  which  is  to  be  saturated  with 
solutions  of  the  albumin  reagents,  and  some  with  citric  acid, 
and  then  drying.  The  papers  are  then  cut  into  slips  of  con- 
venient size  for  testing,  and  may  be  carried  about  in  the  pocket- 
case  for  use  at  the  bedside  of  the  patient.  In  testing,  the  follow- 
ing method  is  followed  :  Into  a  small  test-tube  containing  5  c.c. 
of  distilled  water  are  dropped  a  reagent  paper  and  one  charged 
with  citric  acid.  After  agitation  for  a  minute  or  so  the  test- 
papers  are  removed,  and  the  solution  is  ready  for  testing.  The 
urine  is  now  added  ;  the  test  may  be  conducted  either  by  a  mix- 
ture of  the  two  or  by  the  contact  method,  of  which  Dr.  Oliver 
advises  the  latter. 

Dr.  Oliver  now  recommends  the  use  of  two  reagents  only  for 
albumin — viz.,  the  potassium  ferrocyanideand  potassio-mercuric- 
iodide  papers.  The  former  of  these  will  be  found  trustworthy, 
and  of  very  great  convenience  at  the  bedside. 

The  potassio-mercuric-iodide  test  must,  in  all  cases,  be  con- 
trolled by  heating,  otherwise  it  may  be  misleading. 

The  Removal  of  Albumin  by  Heat. — If  the  urine  to  be 
examined  contains  more  than  a  trace  of  albumin,  it  should 
be  removed  before  testing  for  chlorides,  sulphates,  and 
sugar,  since  the  albumin  either  enters  into  combination 
with  the  reagents  or. reacts  with  them  in  such  a  manner  as 
to  render  the  tests  unreliable.  The  best  method  for  the 
removal  of  albumin  is  to  coagulate  it  by  heat ;  this  should 
be  applied  in  connection  with  both  qualitative  and  quanti- 
tative analyses. 

I.  For  Qualitative  Tests. — Take  one-third  of  a  test- 
tube  of  urine,  add  one  drop  of  dilute  acetic  acid,  and  boil  the 
whole  mixture  thoroughly.  If  a  flocculent  precipitate  does 
not  form,  add  at  intervals,  drop  by  drop,  more  acetic  acid, 
heating  the  mixture  after  each  addition  until  a  distinct  floc- 
culent coagulum  forms.  Filter  ;  the  filtrate  should  be  per- 
fectly clear  and  practically  free  from  albumin. 

■2.  For  Quantitative  Analysis.  —  Take  a  definite 
quantity  of  the  urine,  say  50  c.c,  place  in  a  porcelain  evap- 
9 


130  ABNORMAL  CONSTITUENTS  OF  URINE. 

orating  dish,  add  two  or  three  drops  of  dilute  acetic  acid, 
and  boil  thoroughly.  If  a  flocculent  coagulum  of  albumin 
does  not  appear,  add  a  few  more  drops  of  the  acetic  acid, 
drop  by  drop,  stirring  constantly  and  continuing  the  heat 
until  such  a  flocculent  coagulum  forms.  Filter, — the  filtrate 
should  be  free  from  precipitate, — and  wash  once  or  twice 
with  water.  Allow  the  filtrate  and  wash-water  to  run  into 
a  graduate,  and  add  sufficient  water  to  make  the  original 
volume  (50  c.c).  Mix  the  contents  of  the  graduate  thor- 
oughly, and  use  for  the  quantitative  tests. 

In  removing  albumin  by  heat  a  flocculent  coagulum 
should  be  obtained  in  all  cases,  and  this  is  accomplished 
when  the  urine  has  a  faintly  acid  reaction  (preferably  with 
acetic  acid).  In  case  a  flocculent  coagulum  is  not  obtained, 
the  filtrate  will  be  more  or  less  turbid,  the  turbidity  being 
due  to  the  finely  divided  precipitate  of  albumin.  Such  a 
turbid  filtrate  is  unfit  for  further  tests. 

Quantitative  Estimation  of  Albumin  in  Urine. — Ex- 
pression of  Quantity  of  Albumin  Found  in  Urine. — In 
referring  to  the  quantity  of  albumin  found  in  the  urine  the 
author,  in  all  cases,  means  the  quantity  by  iveigJit,  and  not 
the  bulk  measure  ;  thus,  if  the  expression  "^  of  i  per 
cent."  be  used,  it  is  ^^  of  i  per  cent,  by  weight  that  is 
intended.  We  not  infrequently  read  that  urines  contain  25, 
50,  and  even  75  per  cent,  of  albumin.  The  quantity  by 
bulk  is,  of  course,  intended,  since  3  to  5  per  cent,  by 
w^eight  is  probably  the  maximum  amount  of  albumin  that 
urine  can  contain.  Much  greater  care  should  be  exercised 
in  speaking  of  the  quantity  of  albumin  present,  using  the 
terms  percentage  by  zveiglit  or  percentage  by  bulk,  according 
to  the  meaning  of  the  writer.  Attention  given  this  matter 
will  be  the  means  of  avoiding  much  confusion,  particularly 
to  students. 

The  term  "i  per  mille,"  or  "i  p.  m.,"  refers  to  the  num- 
ber of  grams  of  albumin  contained  in  i  liter  of  urine  ; 
thus,  the  foregoing  expression  equals  i  gram  of  albumin  in 
1000  c.  c.  of  urine,  or  ^  of  i  per  cent,  by  weight ;  2  p.  m. 
equals  2  grams  in  looo  c.  c,  or  -^-^  of  i  per  cent.  ;  5  p.  m. 
equals  5  grams  in  1000  c.  c,  or  i  of  i  per  cent.,  etc. 

Gravimetric  Process. — This  process  for  the  quantita- 
tive estimation  of  albumin  gives  accurate  results,  but  is 
unsuitable  for  clinical  purposes  on  account  of  the  length  of 
time  and  the  apparatus  required  for  its  completion. 


ALBUMIN. 


131 


1f?ifl 


Take  lOO  c.c.  of  the  urine,  place  in  a  beaker  or  glass 
evaporating  dish,  and  heat  on  a  water-bath.  A  two  per 
cent,  solution  of  acetic  acid  is  then  added,  drop  by  drop, 
until,  upon  boiling,  a  flocculent  precipitate  of  albumin 
separates.  This  is  then  filtered  through  an 
ash-free  filter  which  has  been  previously 
dried  and  weighed.  The  precipitate  is 
washed  successively  with  water,  alcohol, 
and  ether,  and  dried  at  a  temperature  of 
120°  to  130°  C.  After  cooling  the  filter 
is  again  weighed,  and  the  difference  in 
weight  due  to  the  precipitate  represents  the 
quantity  of  albumin  in  the  100  c.c.  of 
urine  used. 

Devoto^  recommends  the  following  pro- 
cedure :  Take  a  definite  quantity  of  urine, 
precipitate  the  albumin  with  ammonium 
sulphate,  heat  on  a  water-bath,  and  wash 
the  precipitate  with  boiling  water  until  the 
filtrate  no  longer  becomes  cloudy  on  stand- 
ing, or  upon  the  addition  of  sodium  chloride. 
The  precipitate  is  then  washed  with  alcohol 
and  ether,  and  the  remainder  of  the  process 
conducted  as  previously  directed. 

Esbach's  Method. — This  test  is  made 
by  means  of  a  standard  graduated  glass 
tube  or  albuminometer,^  as  shown  in  figure 
16.  The  process  is  as  follows  :  The  fol- 
lowing solution  is  prepared :  Picric  acid, 
10  grams  ;  citric  acid,  20  grams  ;  distilled 
water,  to  lOOO  c.c.  (i  liter).  Fill  the 
albuminometer  tube  with  the  urine  to  the 
letter  U,  then  add  the  reagent  to  R,  close 
the  tube  with  the  stopper,  and  invert  several 
times,  until  the  urine  and  the  reagent  are 
thoroughly  mixed.  Stand  the  tube  in  a 
rack  for  twenty-four  hours,  and  then  read 
off  the  number  of  grams  of  albumin  to  the  liter,  as  will  be 
indicated  by  the  number  on  the  side  of  the  tube  on  a  level 
where  the  albumin   settles.      If  it  is  desired  to  know  the 


Fig.  16.  —  Esbach's 
albuminometer. 


1  Devoto,  "  Zeitschr.  f.  physiol.  Ch.,"  xv,  474,  1891. 
^  Esbach's  tubes  are  supplied  by  Eimer  &  Amend,  of  Third  Avenue,  New 
York,  at  a  moderate  cost. 


132  ABNORMAL  CONSTITUENTS  OF  URINE. 

percentage  of  albumin  in  the  urine  instead  of  the  number 
of  grams  per  hter,  remove  the  decimal  point  one  figure 
to  the  left;  thus,  5  grams  per  liter  would  be  0.5  per  cent, 
of  albumin.  It  will  be  observed  that  Esbach's  albumin- 
ometer  tubes  are  so  graduated  that  their  highest  range  is 
7  grams  per  liter — 0.7  per  cent,  of  albumin.  If,  therefore, 
the  urine  be  highly  albuminous,  it  should  be  diluted  with 
one  or  two  volumes  of  water  before  testing,  and  the  pro- 
duct multiplied  by  two  or  three,  according  as  the  volume 
is  doubled  or  trebled. 

Centrifugal  Method — Potassium  Ferrocyanide  and 
Acetic  Acid. — Albumin  can  be  readily  precipitated  by 
means  of  a  mixture  of  potassium  ferrocyanide  and  acetic 
acid,  and  quantitated  by  using  the  graduated  tubes  of  a 
centrifugal  apparatus. 

Process. — Take  10  c.c.  of  filtered  urine,  add  3.5  c.c.  of  a 
solution  of  potassium  ferrocyanide  (i  :  10),  and  1.5  c.c. 
of  acetic  acid  (U.  S.  P.) ;  close  the  tube  with  the  thumb, 
and  invert  several  times  in  order  to  mix  thoroughly.  The 
tubes  are  then  placed  in  the  centrifuge,  which  is  revolved 
until  the  precipitate  of  albumin  has  been  completely  set- 
tled and  the  supernatant  fluid  is  perfectly  clear.  The  cen- 
trifuge should  be  run  at  the  speed  of  lOOO  revolutions  per 
minute  and  for  from  three  to  five  minutes.  According  to 
Purdy,  each  -^-^  c.c.  of  precipitate  represents  i  percent,  hulk 
incasiire,  or  volume  per  cent,  of  albumin. 

In  order  to  determine  the  percentage  of  albumin  by 
weight  in  the  use  of  the  above  method  the  writer,  a  few 
years  ago,  made  a  series  of  experiments  which  led  to  the 
following  conclusion  :  each  -^  c.c.  of  precipitate  represc?its 
■^  of  I  per  cent,  of  albumin  by  zveigJit. 

This  method  furnishes  a  very  rapid,  accurate,  and  con- 
venient means  of  quantitating  albumin,  and  is  subject  to 
only  very-  slight  sources  of  error.  The  most  important 
part  of  the  test  is  to  thorougJily  settle  the  precipitate. 

GLOBULIN. 

Serum  globulin,  also  termed  paraglobulin,  is  a  proteid 
which  is  usually  associated  with  serum  albumin,  and  is  fre- 
quently found  in  the  urine.  Globulin  is  insoluble  in  water 
and  soluble  in  dilute  (i  per  cent.)  solutions  of  sodium  chlo- 
ride. It  is  also  soluble  in  dilute  acids  or  alkalies,  being 
changed   into   acid-  and  alkali-proteid    respectively,  unless 


GLOBULIN.  133 

the  acids  and  alkalies  are  exceedingly  dilute  and  their  action 
is  not  prolonged.  It  is  precipitated  by  saturating  its  solu- 
tions with  magnesium  sulphate,  with  sodium  chloride,  and 
by  half-.saturation  with  ammonium  sulphate.  Globulin  can 
be  quantitated  by  saturating  its  neutral  solution  with  magne- 
sium sulphate,  since  the  other  proteids  are  not  precipitated 
by  it.  It  is  partially  precipitated  from  its  solution  by 
carbonic  acid  gas.  When  its  solutions  are  dialyzed,  it  is 
precipitated,  owing  to  the  fact  that  the  percentage  of  salt  is 
so  far  reduced  by  dilution  that  it  is  no  longer  sufficient  to 
hold  the  globulin  in  solution.  Its  dilute  saline  solutions 
coagulate  on  heating  to  75°  C.  (Halliburton). 

Normal  urine  is  free  from  globulin,  but  this  proteid  may 
be  found  in  the  urine  under  pathologic  conditions. 

Clinical  Significance. — The  clinical  significance  of  the 
presence  of  globulin  is  much  the  .same  as  that  of  albumin. 
It  has  been  found  in  abundance  in  amyloid  infiltration  of 
the  kidneys  (in  much  larger  quantities  than  in  other  forms 
of  Bright's  disease — Senator),  acute  nephritis,  chronic  cys- 
titis, pyonephrosis  ^  following  deranged  digestion,  and  in 
the  severe  hyperemia  following  cantharides  poisoning. 
Although  globulin  is  usually  present  in  the  urine  in  much 
smaller  quantities  than  albumin,  it  may  equal  or  even  exceed 
it  in  amount.  It  is  occasionally  found  in  the  urine  when 
albumin  is  absent.  In  severe  organic  disease  of  the  kidneys 
and  in  the  albuminuria  that  occurs  in  diabetes,  Maguire  ^ 
found  that  the  proportion  of  albumin  to  globulin  was  as 
2.5  :  I  (normal  in  the  blood,  L5  :  i). 

Detection. — Saturate  the  urine,  which  has  been  pre- 
viously neutralized  and  filtered,  with  magnesium  sulphate  ; 
a  white  precipitate  results  if  globulin  is  present. 

When  a  few  drops  of  the  globulin-containing  urine  are 
allowed  to  fall  into  a  large  volume  of  distilled  water,  a  tur- 
bidity appears  (nucleo-albumin  gives  a  similar  turbidity)  ; 
when  much  globulin  is  present,  the  water  assumes  a  milky 
opalescence. 

Quantitative  Estimation  of  Globulin. —  Take  100  cc. 
of  the  urine-containing  globulin,  render  neutral  or  faintly 
alkaline  with  amnionic  hydrate,  and  remove  the  precipitated 
phosphates  by  filtration  ;  then  completely  saturate  with 
magnesium  sulphate  ;   filter,  and  wash  with  a  saturated  solu- 

'  "  Boston  Medical  and  Surgical  Journal,"  March  3,  1898,  p.  197. 
2  "  British  Medical  Journal,"  vol.  II,  l886,  p.  543. 


134  ABNORMAL  CONSTITUENTS  OF  URINE. 

tion  of  magnesium  sulphate.  The  entire  precipitate  on  the 
filter-paper  is  then  dissolved  in  water  or  a  weak  solution 
of  sodium  chloride,  and  the  globulin  coagulated  by  boil- 
ing, the  solution  having  been  previously  faintly  acidu- 
lated with  acetic  acid.  The  coagulation  must  be  com- 
plete. Filter  through  a  previously  dried  and  weighed 
filter-paper.  The  filter  containing  the  precipitate  is  then 
dried  at  a  temperature  of  i  io°  to  120°  C,  cooled,  and 
weighed.  The  difference  between  the  filter-paper  and 
filter-paper  plus  precipitate  equals  the  quantity  of  globulin 
in  100  c.c.  of  urine. 

This  test  is  probably  not  perfectly  accurate,  since  small 
amounts  of  other  proteids,  notably  some  forms  ofalbumose,^ 
are  precipitated  by  magnesium  sulphate. 

ALBUMOSES. 

This  proteid  belongs  to  the  general  class  of  proteoses. 
The  albumoses,  together  with  another  proteose, — glohulose, 
— are  absent  from  normal  urine  (except  perhaps  in  the 
slightest  traces),  but  are  occasionally  found  under  patho- 
logic conditions.  Up  to  the  present  time  very  little,  if  any- 
thing, is  known  of  the  clinical  significance  of  the  globu- 
loses,  so  that  they  will  not  be  considered  here. 

The  albumoses  are  formed  by  the  action  of  the  gastric 
and  pancreatic  juices  on  proteid  material,  and  appear  as 
intermediate  products  between  the  proteid  material  and  the 
final  product,  peptone. 

Varieties. — According  to  Kiihne,  there  are  at  least  two 
albumoses — autialdionose,  the  forerunner  o(  antipeptone,  and 
Jiemialbiimose,  the  forerunner  of  heinipeptone.  Of  these  two 
forms  he^nialbiimose  is  the  more  important.  Kiihne  and 
Chittenden,  in  their  earlier  work,^  at  first  distinguished 
between  a  soluble  and  insoluble  form,  but  more  recently 
they  have  described  four  closely  allied,  though  dis- 
tinct forms  of  albumose. ^  (i)  Protalbimiose ,  soluble  in 
hot  and  cold  water  and  precipitated  by  saturation  with 
sodium  chloride  and  magnesium  sulphate.  (2)  Hetcro- 
albiunose,  insoluble  in  hot  and  cold  water,  soluble  in  dilute 
(0.5   per  cent.)  and   in   more   concentrated  (15    per   cent.) 

1  Halliburton,  "Text-book  of  Cheni.,  Physiol.,  and  Pathol.,"  p.  783. 

2  "Zeitschr.   f.  Biol.,"  Bd.  xix,  1883,  S.  174. 

3  Ibid.,  Bd.  XX,  S.  II. 


ALBUMOSES.  135 

solutions  of  sodium  chloride,  but  precipitated  from  these  by 
saturation  with  the  salt.  It  is  precipitated  by  alcohol, 
when  it  is  partly  converted  into  (3)  dysalbumose,  which  is 
insoluble  in  saline  solutions.  (4)  Dciitcro-albiimosc  soluble 
in  hot  and  cold  water,  not  precipitated  by  saturating  with 
sodium  chloride  or  magnesium  sulphate,  unless  an  acid  be 
added  at  the  same  time,  but  is  precipitated  by  saturating 
with  ammonium  sulphate  and  by  nitric  acid,  if  an  excess  is 
not  added. 

Clinical  Significance. — Albumose  was  first  discovered 
in  the  urine  by  Bence  Jones  ^  in  a  case  of  osteomalacia. 
It  has  since  been  found  in  this  disease  by  Kiihne  ^  and 
others.  Virchow  ^  has  found  albumose  in  the  bone-marrow 
in  cases  of  osteomalacia  ;  Hoppe-Seyler  ^  found  it  in  several 
cases  of  atrophy  of  the  kidneys  ;  Lassar  ^  found  it  in  the 
urine  of  people  who  had  been  rubbed  with  petroleum,  and 
Oertel  ^  in  a  few  cases  after  severe  exertion.  Senator  has 
found  albumose  in  the  urine  in  croupous  pneumonia,  diph- 
theria, tertiary  syphilis,  carcinoma,  hemiplegia,  and  muscu- 
lar atrophy.  It  has  been  found  by  a  number  of  observers 
in  sarcomata  of  the  bones  of  the  trunk,  especially  of  the 
ribs  and  sternum.  Fitz  '^  has  reported  a  case  of  myxedema 
in  which  albumosuria  was  a  prominent  feature. 

H.  Senator  ^  has  recently  reported  a  case  of  multiple 
sarcomatosis  of  the  ribs  in  which  albumosuria  was  a  promi- 
nent feature.  His  patient  also  suffered  from  chronic  paren- 
chymatous nephritis  with  amyloid  infiltration  of  the  kidneys, 
fibrinous  pleurisy,  bronchopneumonia,  and  gangrene  in 
the  region  of  the  left  trochanter. 

The  quantity  of  albumose  found  in  the  urine  of  croupous 
pneumonia,  diphtheria,  tertiary  syphilis,  carcinoma,  muscu- 
lar atrophy,  after  severe  exertion,  etc.,  is  usually  very  small, 
it  being  present  only  in  traces  ;  in  cases  of  sarcomata  of 
the  bones  of  the  trunk  the  quantity  may  reach  as  high  as 
^  of  I  per  cent. 

1  "Phil.  Trans.  Roy.  Soc,"  vol.  i,  1848. 

2  "  Zeitschr.  f.  Biol.,"  xix,  S.  209. 
•*  "  Virchow's  Archiv,"  iv,  S.  309. 
*"  Physiol.  Chem.,"    S.  858. 

5  "Virchow's  Archiv,"  Lxxvil,  S.  164. 
*  "  Ziemssen's  Handbuch  d.  Therapie,"    1884. 
'"  American  Jour.  Med.  Sciences,"  July,  1898. 
'  "  Berliner  klin.  Wochenschr. ,"   Feb.  20,  1899. 


136  ABNORMAL  CONSTITUENTS  OF  URINE. 

Although  the  condition  of  albumosuria  has  been 
thoroughly  studied  by  a  number  of  able  chemists  and  clin- 
icians, its  true  clinical  significance,  up  to  the  present  time, 
is  very  indefinite.  The  fact  that  albumose  has  been  so  fre- 
quently found  in  bone  diseases  would  suggest  a  possible 
cause  of  the  condition. 

Detection. — From  a  clinical  point  of  view  it  is  not  essen- 
tial to  distinguish  between  the  various  forms  of  albumose  ; 
the  following  reactions  suffice  for  its  detection  : 

1.  Take  a  small  portion  of  the  urine  in  a  test-tube,  and 
warm  gently.  A  precipitate  appears  which  is  redissolved 
on  boiling  and  reappears  on  cooling. 

2.  Acidulate  the  urine  with  acetic  acid,  and  add  a  few 
drops  of  a  saturated  solution  of  sodium  chloride.  A  pre- 
cipitate is  formed  which  disappears  on  heating  and  reap- 
pears on  cooling. 

3.  Add  a  few  drops  of  nitric  acid  to  the  urine  in  a  test- 
tube.  If  the  acid  is  not  in  excess,  a  precipitate  is  formed 
which  disappears  on  boiling  and  reappears  on  cooling. 

4.  Add  acetic  acid,  avoiding  an  excess,  and  then  a  few 
drops  of  a  solution  of  potassium  ferrocyanide  (i  to  10).  A 
precipitate  is  formed  which  disappears  on  boiling  and  reap- 
pears on  cooling. 

5.  Completely  saturate  the  urine  (preferably,  according 
to  Kiihne,  at  boiling  temperature)  with  neutral  ammonium 
sulphate.  Filter  and  wash  the  precipitate  with  a  saturated 
solution  of  ammonium  sulphate.  Dissolve  the  precipitate 
in  water  or  dilute  sodium  chloride  solution,  and,  if  albumose 
be  present,  its  solution  will  give  the  biuret  reaction.  This 
method  separates  the  albumoses  from  the  peptones,  the 
former  being  precipitated,  the  latter  remaining  in  solution 
and  appearing  in  the  filtrate  from  the  ammonium  sulphate 
precipitate. 

PEPTONE. 

Peptones  are  the  final  products  of  gastric  and  pancreatic 
digestion  of  albuminous  bodies,  in  so  far  as  these  final 
products  are  still  true  albuminous  substances.  When, 
however,  the  digestion  (hydration)  is  continued,  the  pep- 
tones split  up  into  simpler  bodies,  which  are  no  longer 
proteid  in  character.  Peptones  are,  furthermore,  products 
of  pathologic  changes  in  the  blood-corpuscles.  They  may 
also  be  produced  from  albumin  by  the  continued  action  of 


PEPTONE.  137 

acids  and  alkalies,  and  it  is  said,  also,  by  the  decomposin<j 
action  of  bacteria,  as  well  as  the  long-continued  operation 
of  a  temperature  of  130°  to  143°  C. 

Peptones  are  not  coagulated  by  heat.  They  are  not 
precipitated  by  nitric  acid,  ammonium  sulphate,  potassium 
ferrocyanide  and  acetic  acid,  but  are  thrown  down  by  a 
mixture  of  picric  and  citric  acids,  tannic  acid,  phospho- 
molybdic  acid,  phosphotungstic  acid,  potassio-mercuric 
iodide  (Tanret's  reagent),  mercuric  chloride,  and  Millon's 
reagent.  They  are  precipitated,  but  not  coagulated,  by 
alcohol.  Peptone  is  very  soluble  in  water,  and  is  readily 
diffused  through  animal  membranes  ;  albumoses  are  only 
slightly  diffusible. 

Peptones  exist  in  two  forms:  (i)  Hcinipcptoiic,  which  is 
obtained  by  the  action  of  trypsin  on  hemialbumose.  When 
purified  and  digested  with  trypsin  it  yields  much  leucin  and 
tyrosin,  and  in  this  respect  alone  does  it  differ  from  anti- 
peptone.  (2)  Antipcpt07ie  is  formed  as  the  result  of 
digestion  of  antialbumose,  but  is  not  capable  of  yielding 
leucin  and  tyrosin  when  purified  and  subjected  to  the  most 
prolonged  action  of  the  pancreatic  juice.  It,  moreover, 
does  not  yield  leucin  and  tyrosin  when  treated  with 
sulphuric  acid,  and  does  not  react  with  Millon's  reagent. 
Peptone  is  not  present  in  healthy  blood  or  normal  urine. 

Clinical  Significance. — Peptone  was  first  described  in 
the  urine  by  Gerhardt.  ^  Up  to  the  publication  of  the  very 
able  researches  of  Kiihne  and  Chittenden,  most  of  the 
proteids  clas.sed  as  peptones  were  probably  albumoses,  or 
mixtures  of  albumoses  and  peptones,  so  that  the  early  data 
concerning  peptonuria  are  far  from  reliable.  The  proteid 
most  liable  to  be  mistaken  for  peptone  is  deutero-albumose. 
According  to  Maixner,  peptone  is  always  present  in  the 
urine  when  pus  is  forming  in  any  part  of  the  body.  For 
this  reason  peptonuria  is  often  present  in  septicemia,  and  can 
thus  be  distinguished  from  other  conditions  that  are  not  pyo- 
genic. Likewise,  in  acute  inflammatory  diseases,  the  pres- 
ence of  peptone  in  the  urine  usually  indicates  that  suppura- 
tive changes  have  been  established,  other  known  causes  of 
peptonuria  being  absent.  Destruction  of  the  corpuscular 
blood  elements  in  some  of  the  acute  infectious  diseases 
seems    to    be    a   cau.se    of   peptonuria.       According  to   v. 

'  •'  Deutscli.  Arclii\.  f.  klin.  Med.,"  v,  215. 


138  ABNORMAL  CONSTITUENTS  OF  URINE. 

Jaksch,  peptonuria  is  a  constant  accompaniment  of  epidemic 
cerebrospinal  meningitis,  and  is  absent  in  tubercular  menin- 
gitis. This  furnishes  an  important  means  of  distinguishing 
between  these  two  diseases,  providing  suppurative  conditions 
elsewhere  are  excluded. 

A  number  of  observers  have  described  peptonuria  in  a 
variety  of  pathologic  conditions  :  Suppurative  diseases,  em- 
pyema, croupous  pneumonia,  gangrene  of  the  lung,  small- 
pox, erysipelas,  scarlet  fever,  typhoid  fever,  tuberculosis, 
acute  rheumatism,  cancer  of  the  gastro-intestinal  tract  and 
liver,  cerebral  hemorrhage,  phosphorus-poisoning,  typhus, 
etc.  Naturally,  the  accuracy  of  observation  in  connection 
with  some  of  the  above-mentioned  diseases  is  doubted, 
since,  previous  to  the  work  of  Kiihne  and  Chittenden, 
nothing  was  known  of  the  means  of  distinguishing  between 
peptone  and  other  proteids. 

Detection. — The  accurate  detection  of  peptone  depends 
upon  its  separation  from  albumose,  and  this  is  accomplished 
as  follows  :  The  urine,  first  faintly  acidulated  with  acetic 
acid,  is  completely  saturated  with  ammonium  sulphate,  and 
filtered.  The  precipitate  may  consist  of  albumin,  globulin, 
or  albumose.  The  only  proteid  in  the  filtrate,  however,  is 
peptone,  which  can  be  detected  by  the  biuret  reaction,  or 
by  precipitation  with  tannic  acid,  potassio-mercuric  iodide, 
picric  acid,  phosphotungstic  acid,  or  phosphomolybdic  acid. 
According  to  Kuhne,  in  order  to  separate  completely  the 
albumoses  from  the  peptones  the  saturation  with  ammonium 
sulphate  should  be  conducted  at  the  boiling  temperature. 
Furthermore,  a  single  saturation  with  ammonium  sulphate 
should  not  be  depended  upon  for  the  removal  of  all  of  the 
albumose,  but  saturation  should  be  repeated  until  precipita- 
tion fails  to  occur. 

Separation. — Chittenden  recommends  the  following  pro- 
cess for  the  separation  of  the  peptone  from  the  ammonium 
sulphate  saturated  solution.  The  fluid  is  concentrated 
somewhat,  and  set  aside  in  a  cool  place  for  the  crystalliza- 
tion of  a  portion  of  the  ammonium  salt.  The  fluid  is  then 
mixed  with  about  one-fifth  of  its  volume  of  alcohol,  and 
allowed  to  stand  for  some  time,  when  it  separates  into  two 
layers,  an  upper  one  rich  in  alcohol,  and  a  lower  one  rich 
in  salts.  The  latter  is  again  treated  with  alcohol,  by  which 
another  separation  of  the  same  order  is  accomplished.  The 
lighter  alcoholic  layers  containing  the  peptone  are  united 


PEPTONE.  139 

and  exposed  to  a  low  temperature  until  considerable  of  the 
contained  salt  crystallizes  out.  The  fluid  is  then  concen- 
trated, and  after  the  addition  of  a  little  water  is  boiled  with 
barium  carbonate  until  the  fluid  is  entirely  free  from  ammo- 
nium sulphate.  Any  excess  of  baryta  in  the  filtrate  is 
removed  by  the  cautious  addition  of  sulphuric  acid,  after 
which  the  concentrated  fluid,  reduced  almost  to  a  syrupy 
mass,  is  poured  into  absolute  alcohol  for  the  precipitation 
of  the  peptone. 

Biuret  Reaction. — Take  a  small  portion  of  the  fluid  to  be 
tested  in  a  test-tube,  add  an  excess  of  sodic  hydrate,  and  then  add, 
drop  by  drop,  a  dilute  solution  of  copper  sulphate.  The  charac- 
teristic reaction  is  the  appearance  of  a  rose-red  color.  Great  care 
must  be  exercised  in  the  addition  of  the  copper  solution,  since  an 
excess  of  it  gives  a  reddish-violet  color,  which  is  often  misleading. 

The  substances  in  the  urine  which  give  the  characteristic 
biuret  reaction  are  albiimoses,  peptones,  and  tirobilin.  Since 
more  or  less  urobilin  is  present  in  every  urine,  it  must  be 
thoroughly  removed  before  this  test  can  be  satisfactorily  applied 
for  the  detection  of  albumoses  and  peptone. 


METHOD  OF  SEPARATION  AND  IDENTIFICATION  OF 
PROTEIDS. 

The  following  table,  proposed  by  Halliburton,  ^  gives  the 
method  for  separating  serum  albumin,  serum  globulin, 
albumoses,  and  peptone,  should  they  happen  to  be  present 
together  in  the  urine.  This  is  a  very  rare  occurrence,  but 
in  doubtful  cases  it  is  best  to  test  for  every  one  in  the  list  : 

1.  If  the  urine  gives  no  precipitate  on  boiling  after 
faintly  acidulating  with  acetic  acid,  albumin  and  globulin 
are  absent.  If  a  precipitate  occurs,  albumin  or  globulin  or 
both  are  present. 

2.  If  the  urine  after  neutralization  gives  no  precipitate  on 
saturation  with  magnesium  sulphate,  globulin  and  hetero- 
proteose  are  absent.  If  such  a  precipitate  occurs,  one  or 
the  other  is  present. 

3.  If  the  urine  be  saturated  with  ammonium  sulphate 
and  filtered,  and  the  filtrate  gives  no  xanthoproteic  or  biuret 
reaction,  peptone  is  absent. 

4.  If  the  urine  gives  no  precipitate  on  boiling  after  acidu- 
lation,  no  precipitate  with  nitric  acid,  and  no  precipitate  on 

^  "Text-book  of  Chem.,  Physiology,  and  Pathology,"  p.  788. 


140  ABNORMAL  CONSTITUENTS  OF  URINE. 

adding  ammonium  sulphate  to  saturation,  peptone  can  be 
the  only  proteid  present.  Confirm  this  by  the  biuret  reac- 
tion. 

5.  If  all  proteids  are  present,  they  may  be  separated  as 
follows  : 

Saturate  the  urine  (faintly  acidified  with  acetic  acid)  with 
ammonium  sulphate.      A  precipitate  is  produced.      Filter. 

(")    Precipitate.  .  (^^   Filtrate. 

Contains  albumin,  globulin,    het-  Contains  peptone, 

and    deuteropioteose.      Collect 


the  precipitate  on  a  filter,  wash  it  with  saturated  solution  of  ammonium  sul- 
phate, and  redissolve  it  by  adding  a  small  quantity  of  water.  To  this  solution 
add  ten  times  its  volume  of  alcohol  ;  a  precipitate  is  formed  ;  collect  this,  and 
let  it  stand  in  absolute  alcohol  for  from  seven  to  fourteen  days.  Then  filter 
off  the  alcohol,  dry  the  precipitate  at  40°  C,  extract  it  with  water,  and  filter. 
An  insoluble  residue  is  left. 

(<?)   Residue.  I  [h)   Extract. 

This  consists  of  albumin  and  glob-  This  contains  the  proteoses  in  solu- 

ulin  coagulated  by  the  alcohol.  tion. 

Heterocaseose  is  precipitated  by  heating  the  solution  to  65°  C,  or  by  satu- 
rating a  portion  of  the  extract  with  magnesium  .sulphate.  Deuteroproteose 
remains  in  solution. 


Take  another  portion  of  urine,  neutralize  it,  and  saturate  with  magnesium 
sulphate.      A  precipitate  is  produced.      Filter. 

(rt)   Precipitate.  I  {b)   Filtrate. 

This  consists  of  globulin  and  het-    j  This    contains    albumin,    deutero- 

eroproteose,  which  may  be  separated  proteose,  and  peptone.  Add  alcohol 
by  the  prolonged  use  of  alcohol,  as  |  as  above  ;  albumin  is  rendered  in.solu- 
above.  1    ble  in  water  in  from  .seven  to  ten  days. 

The  deuteroproteose  and  peptone  are 
soluble,   and  may  then  be    separated 
I    by  ammonium  sulphate. 


NUCLEO-ALBUMIN  (MUCIN?) 

A  true  nucleo-proteid,  or  nucleo-albumin  is  a  combination 
of  a  nuclein  with  more  albuminous  matter.  ^  This  form  of 
proteid  formerly  known  as  mucin  is  probably  not  true 
mucin.  The  presence  of  small  quantities  of  nucleo-albumin 
in  the  urine  occurs  under  normal  conditions,  it  being  a  pro- 
duct of  the  secretion  of  the  cells  lining  the  urinary  tract. 
This  substance  is  probably  identical  with  the  nucleo-albu- 
min of  bile. 

^  A  nuclein  is  a  combination  of  some  form  of  proteid  matter  with  a  nucleic 
acid  (Chittenden). 


NUCLEO- ALBUMIN.  141 

Native  nuclco-albumins  contain  approximately  1.5  per 
cent,  of  phosphorus,  are  amorphous,  and  insoluble  in  water, 
but  they  dissolve  in  weak  solutions  of  the  neutral  salts. 
They  are  completely  precipitated  by  saturating  their  solu- 
tions with  ammonium  sulphate,  and  only  incompletely  pre- 
cipitated when  their  solutions  are  saturated  with  magnesium 
sulphate,  or  sodium  chloride.  They  are  soluble  in  alkaline 
hydrates  and  carbonates,  and  are  readily  precipitated  from 
these  alkaline  solutions  by  means  of  strong  mineral  acids. 
They  are,  however,  soluble  in  acetic  acid  and  dilute  mineral 
acids,  and  in  this  respect  they  differ  from  the  nucleins. 

When  nucleo-albumin  is  dissolved  in  a  solution  of  so- 
dium chloride  and  boiled,  a  precipitate  separates.  It  is 
precipitated  by  all  of  the  reagents  used  for  the  precipita- 
tion of  albuminous  bodies,  and  gives  all  of  the  color  reac- 
tions of  proteid  substances.  When  nucleo-albumin  is 
repeatedly  dissolved  and  precipitated,  it  becomes  decom- 
posed, with  the  separation  of  a  portion,  which  is  rich  in 
phosphorus.  When  it  is  subjected  to  the  action  of  pepsin- 
hydrochloric  acid,  it  furnishes  a  proteid  and  insoluble  nu- 
clein.  When  some  of  the  nucleo-albumins  are  boiled  with 
moderately  dilute  mineral  acids,  a  substance  is  produced 
which  reduces  an  alkaline  solution  of  cupric  oxide  with  a 
resulting  brown  color. 

Clinical  Significance. — Nucleo-albumin  has  been  repeat- 
edly found  in  increased  proportion  in  the  urine  of  women, 
in  which  case  it  is  derived  chiefly  from  the  genital  tract.  It 
is  also  found  in  increased  amounts  in  urine  that  has  passed 
over  the  irritated  mucous  membrane  of  some  portion  of  the 
urinary  tract.  Such  a  urine  is  usually  turbid  when  passed, 
and  in  a  short  time  deposits  a  bulky  cloud,  usually  found 
to  contain  a  small,  and  sometimes  a  large,  number  of 
leucocytes,  red  blood-globules,  and  epithelial  cells.  It  was 
first  found  in  large  quantities  by  Miiller  in  the  urine  of 
leukemia,  and  afterward  by  Malfutti  and  others  in  diphtheria, 
scarlatinal  nephritis,  cystitis,  and  after  the  use  of  pyrogallic 
acid,  naphthol,  and  corrosive  sublimate.  It  was  also 
observed  by  Obermayer  in  the  urine  of  a  case  of  acute 
atrophy  of  the  liver.  Ott  found  it  in  abnormal  quantities 
in  the  urine  during  high  fever.  Nucleo-albumin  is  always 
present  in  increased  quantities  in  urine  that  contains  bile. 

Detection. — For  the  detection  of  nucleo-albumin  the 
urine  is  treated  with   an  excess  of  acetic  acid,  when  it  is 


142  ABNORMAL  CONSTITUENTS  OF  URINE. 

rendered  turbid  if  much  of  this  proteid  be  present.  In 
testing  a  concentrated  urine  for  nuclco-albumin  it  is  advis- 
able to  dilute  it  before  acidulating,  on  account  of  the  high 
proportion  of  salts,  which  retain  nucleo-albumin  in  solution 
even  in  the  presence  of  an  excess  of  acetic  acid.  In  testing 
for  the  presence  of  nucleo-albumin  in  an  albuminous  urine 
it  is  necessary  first  to  remove,  by  boiling,  the  great  bulk 
of  the  serum  albumin,  and  any  serum  globulin  present. 
The  fluid  is  then  filtered,  and  allowed  to  cool  before  testing 
with  acetic  acid. 

Ott's  method  for  the  detection  of  nucleo-albumin  is 
very  serviceable  :  To  the  urine  add  an  equal  quantity  of 
saturated  salt  solution  (NaCl),  and  then  Almen's  tannin 
solution  1  is  slowly  added.  If  nucleo-albumin  be  present, 
even  in  small  amounts,  an  abundant  precipitate  will  fall. 

Von  Jaksch  recommends  for  the  precipitation  of  nucleo- 
albumin  a  solution  of  acetate  of  lead. 

HEMOGLOBIN. 

Hemoglobin  is  the  pigment  of  the  red  blood-corpuscles. 
It  gives  the  reactions  of  a  proteid,  but  differs  from  proteids 
in  containing  iron  and  in  being  crystallizable.  It  belongs 
to  the  group  of  compound  proteids,  and  yields  as  cleavage 
products,  besides  very  small  amounts  of  volatile  fatty  acids 
and  other  bodies,  chiefly /n^toV/  (96  per  cent.)  and  a  color- 
ing-matter, licnwchroDwgen  (4  per  cent.)  containing  iron, 
which  in  the  presence  of  oxygen  is  readily  oxidized  into 
hcniatiii  (Hammarsten). 

Hemoglobin  is  found  in  two  forms — /.  c.  {a),  oxyhemo- 
globin, that  charged  with  oxygen  and  found  in  arterial 
blood,  and  presenting,  in  dilute  solutions,  two  absorption 
bands  between  Frauenhofer's  lines  D  and  E ;  and  {b),  reduced 
licjnoglobin,  that  deprived  of  its  oxygen  and  found  in  venous 
blood,  and  presenting  a  single  absorption  band  between 
D  and  E,  occupying  a  space  about  midway  between  the  two 
bands  of  oxyhemoglobin. 

For  further  details  concerning  this  subject  see  page  230. 

^  Aln!en''s  iannin  solution  consists  of:  Tannin,  5  grams;  25  per  cent, 
acetic  acid,  loc.c.  ;  40  to  50  per  cent,  methylated  spirit,  250  c.c. 


FIBRIN.  143 


FIBRIN. 


Fibrin  is  the  albuminous  body  that  separates  on  the 
so-called  spontaneous  coagulation  of  blood,  lymph,  and 
transudations,  as  also  on  the  coagulation  of  a  fibrin- 
ogen solution  after  the  addition  of  blood-serum  or  the 
fibrin  ferment.  It  is  an  elastic,  white,  stringy  substance, 
which  is  insoluble  in  water,  ether,  and  alcohol.  It  is  sol- 
uble with  difficulty  in  solutions  of  sodium  chloride  (5  to  15 
per  cent.),  in  solutions  of  potassium  nitrate  (6  per  cent.), 
and  in  solutions  of  magnesium  sulphate  (5  to  10  per  cent.). 
The  substance  that  goes  into  solution  when  fibrin  is  dis- 
solved in  saline  solutions  is  undoubtedly  a  proteid  of  the 
globulin  class.  It  is  coagulated  by  heat,  precipitated  from 
its  solutions  by  saturating  them  with  magnesium  sulphate, 
and  also  by  dialyzing  away  the  salt  from  such  solutions. 
The  temperature  of  coagulation  is  60°  to  75°  C.  in  a 
sodium  chloride  solution,  and  y^°  to  75°  C.  in  a  magnesium 
sulphate  solution.  Weak  hydrochloric  acid  (0.2  per  cent.) 
causes  fibrin  to  swell  up  into  a  transparent  jelly.  Fibrin  is 
slowly  dissolved  by  the  strong  acids,  with  the  formation  of 
acid  albumin  or  syntonin,  and  albumoses.  Fibrin  is  readily 
digested  by  pepsin  in  the  presence  of  hydrochloric  acid 
(0.2  per  cent.),  and  by  the  pancreatic  juice,  with  the  result- 
ing formation  of  albumoses  and  peptone.  Fibrinogen, 
which  has  also  been  found  to  have  the  properties  character- 
istic of  globulin,  is  the  fibrin-precursor  in  blood  plasma. 

Clinical  Significance. — Fibrin  most  commonly  appears 
in  the  urine  as  an  accompaniment  of  blood,  whether  the 
blood  comes  from  the  kidneys  or  some  other  part  of  the 
urinary  tract.  Usually,  if  there  is  an  extensive  hemorrhage 
into  the  urinary  tract,  fibrin  is  abundant,  and,  on  the  other 
hand,  if  only  little  blood  is  present,  the  quantity  of  fibrin  is 
small.  But  fibrin  may  be  present  in  the  urine  when  blood- 
corpuscles  are  absent ;  thus,  the  so-called  coagnlable  tirinc, 
which,  upon  standing  some  time,  forms  the  fibrinous 
coagula.  The  extent  of  coagulation  depends  upon  the 
quantity  of  fibrin  present ;  sometimes  only  a  sticky  sedi- 
ment forms  in  the  bottom  of  the  sediment-glass ;  more 
rarely,  the  urine  is  converted  into  a  gelatinous  mass. 

Detection, — Fibrin  is  insoluble  in  water  ;  it  is  also  insol- 
uble in  sodic  hydrate,  in  which  respect  it  differs  from  albu- 
minous substances.    If  washed,  fibrin  is  dissolved  in  a  solu- 


144  ABNORMAL  CONSTITUENTS  OF  URINE. 

tion  of  sodic  carbonate  (one  per  cent.)  with  the  aid  of  gentle 
heat,  and  its  solution  gives  the  xanthoproteic  and  Millon's 
reaction  for  proteids.  It  is  readily  digested  by  artificial 
gastric  juice. 

Fibrin  should  not  be  mistaken  for  the  grayish,  ropy  mass 
that  usually  forms  in  purulent,  alkaline  urines,  alkaline 
from  the  ammonia  and  ammonium  carbonate  resulting  from 
the  decomposition  of  the  urea.     (See  p.  237.) 


CHAPTER  V. 

CARBOHYDRATES. 

The  carbohydrates,  which  are  either  normally  or  abnor- 
mally present  in  urine,  resemble  one  another  in  a  few  of 
their  chemic  characteristics.  All  are  hydrocarbons  con- 
taining six  atoms  of  C,  or  a  multiple  thereof;  excepting 
inosite,  all  have  a  strong  rotary  power  over  polarized  light, 
are  soluble  in  water,  and  have  a  neutral  reaction. 

Normal  urine  under  physiologic  conditions  contains  a 
small  amount  of  carbohydrates,  among  which  are  animal 
gum  and  also  grape-sugar,  but  in  amounts  which  can 
not  be  recognized  by  the  ordinary  sugar  reactions.  The 
glucoside — mucin — increases  the  proportion  of  carbohy- 
drates in  the  urine. 

Glucose,  lactose,  levulose,  cane  sugar,  inosite,  glyco- 
gen, and  the  like  are  not  infrequently  found  abnormally  in 
amounts  sufficient  to  respond  to  certain  chemic  tests,  and 
under  such  circumstances  they  are  of  pathologic  interest. 
The  most  important  of  these,  from  a  clinical  point  of  view, 
isglucose. 

GLUCOSE. 

CoH].,Oa. 

(Diabetic  Sugar,  Dextrose,  Grape-sugar.) 

Careful  chemic  examinations  have  shown  it  to  be  highly 
probable  that  normal  urine  contains  traces  of  sugar.  ^ 
Under  pathologic  conditions  glucose  is  present  either 
temporarily — glycosuria — or  permanently — diabetes  mej- 
litus.      (See  Diabetes   Mellitus,  p.  368.) 

Glucose  crystallizes  in  colorless,  transparent  prisms, 
which  collect  in  bundles  or  in  hard,  tenacious  crusts.  It  is 
soluble  in  its  own  weight  of  water,  slightly  soluble  in  cold 

^  Neubauer  and  Vogel,  "  Analyse  des  Hams,"  Bd.  i,  1898,  S.  62. 
10  145 


146  ABNORMAL  CONSriTUENTS  OF  URINE. 

alcohol,  more  readily  in  hot  alcohol,  and  insoluble  in  ether. 
Animal  charcoal  extracts  it  from  its  solutions  (Bence  Jones  ^ 
and  Seegen^).  Solutions  of  glucose  turn  the  rays  of  polar- 
ized light  to  the  right  (dextrose),  and,  according  to  the  last 
accurate  determinations  of  ToUens,  ^  the  specific  rotation  of 
the  aqueous  solution  was  found  to  be  +  52.5°.  In  alka- 
line solutions  it  reduces  the  salts  of  copper,  bismuth, 
mercury,  and  silver  ;  in  the  copper  tests  the  cupric  oxide 
is  reduced  to  cuprous  oxide  (suboxide  of  copper).  Glu- 
cose forms  an  osazone  with  phenylhydrazin, — phenylgluco- 
sazone  (Plate  4),  which  crystallizes  in  highly  characteristic 
groups  of  yellow  needles. 

Isolation. — Grape-sugar  may  be  separated  from  the 
urine  in  a  number  of  ways,  but  the  most  practical  method 
is  that  advised  by  Salkowski.^ 

Salkowskis  Method. — Take  20  c.c.  of  urine  and  add 
10  c.c.  of  a  1.6  normal  solution  of  copper  sulphate  (with 
199.52  grams  of  copper  sulphate  to  the  liter),  and  17.6  c.c. 
of  normal  sodic  hydrate.  After  twenty  to  thirty  minutes, 
dilute  with  100  c.c.  water,  and  filter.  When  the  fluid  has 
passed  through,  the  filter-paper  is  immediately  placed  on 
bibulous  paper  and  entirely  freed  from  the  rest  of  the  fluid. 
The  precipitate  is  then  dissolved  in  50  c.c.  of  dilute  hydro- 
chloric acid  (i  of  hydrochloric  acid,  specific  gravity  1 120,  to 
10  of  water),  the  copper  removed  by  sulphureted  hydro- 
gen, the  filtrate  exactly  neutralized  with  sodic  carbonate, 
and  evaporated  to  20  c.c.  This  fluid  is  then  to  be  tested 
for  sugar,  either  qualitatively  or  quantitatively.  Salkowski 
claims  that  0.5  per  cent,  of  sugar  can  be  detected  in  urine 
in  this  way.  Einhorn  has  detected  as  little  as  0.05  per  cent, 
of  sugar  by  this  method. 

Detection  of  Sugar  in  Urine. — The  copper  tests,  which 
depend  upon  the  power  that  grape-sugar  possesses  in  alka- 
line solution  of  reducing  the  oxide  of  copper  to  lower 
oxides,  are  perhaps  more  commonly  used  than  all  others 
for  the  detection  of  sugar  in  the  urine.  It  is  safe  to  say 
that  they  are  the  most  convenient  and  rapid  of  all  tests  that 
are  capable  of  being  applied  by  the  student  and  practitioner 
of  medicine. 

1  '•  Lancet,"  I,  l86l,  No.  3. 

2  "Pfiuger'.s  Archiv,"  V,  375,  1872. 

3  "  BericlUe  der  chem.  Gesell.sch.,"  xvu,  2234,  1884. 
*"Zeitschr.  f.  physiol.  Ch.,"  \\\,  96,  1879. 


GLUCOSE.  147 

The  oldest  of  the  copper  tests  is  Trommer's,  in  which 
the  hydrate  of  copper  is  set  free  at  the  time  of  its  apphca- 
tion  by  an  excess  of  sodic  or  potassic  hydrate. 

Trommer's  Test. —  i.  Take  a  third  of  a  test-tube  of 
urine,  render  alkahne  with  sodic  or  potassic  hydrate.  To 
this  mixture  then  add,  drop  by  drop,  a  weak  solution  (five 
per  cent.)  of  sulphate  of  copper,  shaking  the  mixture  after 
each  addition,  until  a  deep-blue  solution  is  obtained,  or  until 
the  cupric  hydrate,  which  forms  as  the  copper  is  added,  fails 
to  dissolve.  The  upper  one-half  of  the  mixture  is  then 
boiled,  and  if  sugar  be  present,  a  yellow  precipitate  of  sub- 
oxide of  copper  soon  forms. 

2.  A  second  similarly  prepared  mixture  of  these  ingre- 
dients may  be  made  and  set  aside  for  from  six  to  twenty- 
four  hours  without  the  addition  of  heat.  If  sugar  be 
present,  a  similar  precipitate  of  cuprous  oxide  will  take 
place.  If  the  reaction,  with  heat,  is  at  all  doubtful,  it  is 
important  that  this  control-test  should  be  made,  since,  as 
Neubauer  has  pointed  out,  most  of  the  organic  substances 
that  reduce  copper  do  so  only  when  heated  or  after  pro- 
longed boiling. 

Fehling's  Test. — This  test  is  performed  by  the  use  of 
Fehling's  solution,  which  is  prepared  according  to  the 
original  fonmila,  as  follows  :  Pure  crystallized  cupric  sul- 
phate, 34.639  grams  ;  a  solution  of  caustic  soda, — specific 
gravity  1120, — about  500  c.c.  ;  chemically  pure  crystallized 
neutral  sodic  tartrate,  173  grams.  Prepare  by  dissolving 
the  sulphate  of  copper  in  100  c.c.  of  distilled  water;  next 
dissolve  the  neutral  sodic  tartrate  in  the  solution  of  caustic 
soda,  and  add  the  copper  solution,  little  by  little  ;  finally, 
bring  the  whole  volume  to  1000  c.c.  (i  liter)  with  distilled 
water.  Ten  cubic  centimeters  of  this  solution  require  50 
milligrams  of  sugar  to  completely  reduce  it. 

It  is  a  well-known  fact  that  Fehling's  solution  prepared 
in  the  manner  described  soon  decomposes  on  standing, 
and  therefore  becomes  unfit  for  use.  Furthermore,  it  has 
been  found  (Soxhlet)  that  the  solution  as  previously  given  is 
too  concentrated  to  obtain  a  delicate  reaction.  The  folloiv- 
ing  modificatioi  of  Fchling' s  solution  is  tJwrcfore  nroiu- 
mendcd  for  the  purpose  of  obtaining  a  permanent  solution, 
and  one  which  also  furnishes  a  rapid  and  yet  delicate  reac- 
tion. The  solution  is  divided  into  two  parts — viz.,  copper 
solution  (A)  and  alkaline  tartrate  solution  (B). 


148  ABNORMAL  CONSTITUENTS  OF  URINE. 

A.  Cupric  sulphate 34.639  grams. 

Distilled  water ad     1000  c.c. 

B.  Sodio-potassium  tartrate  (Rochelle  salt)    .     173  grams. 
Sodic  hydrate  (specific  gravity  Il20)i  .    .     500          c.c. 
Distilled  water ad      1000  '• 

These  solutions — A  and  B — are  to  be  kept  in  separate 
bottles  and  in  a  dark  place.  Equal  parts  of  the  two  solu- 
tions produce  diluted  Fehling's  solution.  It  will  be  seen 
that  the  combined  volume  of  the  two  solutions  amounts  to 
2000  c.c,  or  one-half  the  strength  of  the  solution  of  the 
original  formula.  Therefore,  20  c.c.  of  the  combined  mix- 
ture (10  c.c.  of  each)  require  50  milligrams  of  sugar  to 
completely  reduce  it. 

Process. — Qualitative  Test. — Take  equal  parts  of  the 
two  solutions — A  and  B,  about  one  fingerbreadth  of 
each — in  a  test-tube,  and  boil.  If  the  Fehling's  solution 
remains  clear  on  boiling,  then  add  20  to  30  drops  of  the 
suspected  urine  which  is  free  from  albumin.  Do  not  boil 
after  the  addition  of  the  urine.  If  much  sugar  be  pres- 
ent, a  yellow  or  red  precipitate  of  suboxide  of  copper 
readily  appears.  In  case  the  quantity  of  sugar  in  the  urine  is 
less  than  i  per  cent,  the  reduction  will  not  appear  until  after 
several  minutes — five  to  thirty.  If  a  reduction  does  not 
take  place  in  thirty  minutes,  it  is  advisable  to  let  the  test 
stand  for  from  eighteen  to  twenty -four  hours,  since  traces 
of  sugar  show  evidence  of  a  reduction  of  the  copper  only 
after  several  hours,  when  a  small  amount  of  the  suboxide 
will  be  found  in  the  bottom  of  the  test-tube.  Less  time  is 
required  for  the  test  if  the  urine  is  gently  heated  previous 
to  its  being  added  to  the  boiling  Fehling's  solution.  The 
nonappearance  of  a  suboxide  precipitate  shows  that  the 
urine  is  free  from  sugar. 

In  the  hands  of  the  author  Fehling's  test,  performed  in 
the  manner  previously  indicated,  is  one  of  the  most  delicate 
and  reliable  tests  available  for  routine  work.  The  phenylhy- 
drazin  test  is  more  delicate  than  Fehling's,  but  is  less  suit- 
able for  routine  examinations  on  account  of  the  length  of 
time  required  for  the  performance  of  the  test.  (See  p. 
150.) 

If  the  two  solutions,  which  constitute  Fehling's  solution, 
are  kept  in  separate  bottles  and  mixed  at  the  time  they  are 

^  Sodic  hydrate,  having  a  specific  gravity  of  1 120,  is  prepared  as  follows: 
Caustic  soda,  52.727  grams  ;  distilled  water,  sufficient  to  make  5cx)  c.c. 


GLUCOSE.  149 

to  be  used,  there  need  be  no  fear  that  the  solutions  will 
decompose,  even  after  keeping  them  several  months. 

Professor  Haines,  of  Chicago,  has  advised  a  modification 
of  Fehling's  solution,^  and  claims  that  the  solution  prepared 
according  to  his  formula  is  stable,  and,  although  kept  on 
hand  indefinitely,  it  may  always  be  depended  upon  to  be 
in  good  order  for  testing. 

Haines'  Test  {Simplified  Foruiuhx). — Take  pure  copper 
sulphate,  30  grains  ;  distilled  water,  ^^  of  an  ounce  ;  make  a 
perfect  solution,  and  add  pure  glycerin,  y^  of  an  ounce  ; 
mix  thoroughly,  and  add  5  ounces  of  liquor  potassse.  In 
testing  with  this  solution  take  about  i  dram  and  gently  boil 
it  in  an  ordinary  test-tube.  Next  add  6  to  8  drops  (not 
more)  of  the  suspected  urine,  and  again  gently  boil.  If 
sugar  be  present,  a  copious  yellow  or  yellowish-red  precipi- 
tate separates  ;  if  no  such  precipitate  appears,  sugar  is  absent. 

On  account  of  the  decomposition  of  Fehling's  solution 
on  standing,  Schmiedeburg  has  suggested  the  substitution 
of  I  5  grams  of  pure  maiinite  for  the  neutral  sodic  tartrate 
of  Fehling's  solution.  The  mannite  should  first  be  dis- 
solved in  100  c.c.  of  distilled  water,  then  500  grams  of  the 
solution  of  caustic  soda,  specific  gravity  1 140,  should  be 
added,  and  the  solution  completed  according  to  the  original 
formula  for  Fehling's  solution. 

With  the  same  end  in  view  173  grams  of  pure  glycerin 
have  likewise  been  substituted  for  the  neutral  sodic  tartrate 
of  Fehling's  solution. 

When  the  proper  precautions  are  observed,  reliable  re- 
sults may  be  expected  with  Fehling's  solution,  with  saccha- 
rine urine  which  contains  about  -^-^  of  i  per  cent,  of  sugar. 

Precautions  and  Errors. — These  are  applicable  to  all  cop- 
per tests  : 

1.  If  the  urine  contains  more  than  a  trace  of  albumin,  it 
must  be  removed,  as  it  interferes  with  the  reduction  of  the 
oxide  of  copper. 

2.  When  the  mixture  of  urine  and  reagent  is  allowed  to 
stand  several  hours  without  boiling,  a  considerable  quantity 
of  sugar  is  necessary  before  a  satisfactory  reaction   occurs. 

3.  The  mixed  urine  and  reagent  should  never  be  heated 
or  boiled,  since,  as  already  stated,  there  are  often  organic 
substances  other  than  sugar  in  the  urine,  which  have,  in  the 

^  Purely,  "  Practical  Urinalysis,"  p.  103. 


150  ABNORMAL  CONSTITUENTS  OF  URINE. 

presence  of  heat,  a  reducing;  action  on  an  alkaline  solution 
of  cupric  oxide.  These  substances  are  uric  acid,  urates, 
kreatinin,  hippuric  acid,  mucin,  hypoxanthin,  glycuronic 
acid,  alcapton,  alkaloids,  arsenic,  and  carbolic  acid.  Uric 
acid  is  the  chief  source  of  error,  and  should  always  be 
b(jrne  in  mind  in  the  use  of  the  copper  tests. 

4.  The  flocculent  precipitate  of  earthy  phosphates  that  is 
thrown  down  by  the  alkaline  hydrate  should  not  be  mis- 
taken for  the  suboxide  of  copper.  Such  a  precipitate  is 
either  colorless  or  of  a  greenish  hue. 

5.  Decolorization  of  the  reagent  by  the  urine  should  not 
be  mistaken  for  a  reduction  of  the  copper.  There  must  be 
an  actual  yellow  or  red  precipitate.  Any  highly  acid 
normal  or  pathologic  urine  may  have  a  decolorizing  action 
on  the  copper  reagent. 

6.  Too  strong  a  solution  of  copper  should  not  be  used, 
since,  in  the  presence  of  heat,  a  yellow  or  greenish-yellow 
color  is  often  produced.  This  color  may  not  appear  until 
the  mixture  has  cooled. 

Phenylhydrazin  Test- — The  phenylhydrazin  test  for 
sugar  is  applied  as  follows  :  To  50  c.c.  of  the  suspected 
urine  add  i  or  2  grams  of  hydrochlorate  of  phenyl- 
hydrazin, 2  grams  of  sodium  acetate,  and  heat  on  a 
water-bath  for  one  hour  ;  or  add  10  to  20  drops  of  pure 
phenylhydrazin  and  an  equal  number  of  drops  of  50  per 
cent,  acetic  acid,  and  heat  as  before.  On  cooling,  if  not 
before,  pJioiylghicosazonc  separates  out  as  a  crystalline  or 
amorphous  precipitate.  If  upon  microscopic  examination 
the  precipitate  is  found  to  be  amorphous,  it  is  dissolved  in 
hot  alcohol,  and  the  solution  diluted  with  water,  and  boiled 
to  expel  the  alcohol,  whereupon  the  compound  is  obtained 
in  the  characteristic  form  of  yellow  needles.  It  is  claimed 
that  by  this  method  it  is  possible  to  obtain  the  crystals  from 
a  urine  that  contains  only  o.  5  gram  of  sugar  per  liter,  or 
0.05  per  cent. 

Williamson  has  modified  the  phenyl h)'drazin  test  for 
sugar,  as  described  in  the  work  on  urinary  analysis  by 
Hoffmann  and  Ultzmann,  and  has  found  it  very  useful. 

Williamson's  Test.^ — "A  test-tube  of  ordinary  size  is 
filled  for  about  half  an  inch  with  hydrochlorate  of  phenyl- 
hydrazin  (in  powder) ;  then  acetate  of  soda  in  powder  (or 

1  Williamson,"  Diabetes  Mellitus  and  its  Treatment,"  1898,  p.  25. 


Plate  4 


Crystals  of  PiiKNYLGLacosAZONE  (after  vonJaksch). 


GLUCOSE.  151 

small  crystals)  is  added  for  another  Jialf-iiicJi.  Tlie  test- 
tube  is  then  half  filled  with  urine,  and  boiled  over  a  spirit- 
lamp.  In  performing  the  test  I  have  not  attempted  to  dis- 
solve the  salts  by  shaking  the  tube,  but  have  simply  applied 
the  flame  of  the  lamp  to  the  bottom  of  the  tube,  and  the 
powders  have  soon  passed  into  solution.  After  the  urine 
has  reached  the  boiling-point  I  have  always  continued  to 
boil  for  about  tzvo  viimitcs.  The  tube  is  then  left  in  the 
test-stand,  and  examined  again  some  time  afterward." 

If  sugar  be  present,  a  yellowish  deposit  forms  at  the 
bottom  of  the  tube,  and  on  microscopic  examination  it  is 
seen  to  consist  chiefly  of  beautiful  needle-shaped  crystals 
of  a  bright  sulphur-yellow  color.  If  no  sugar  is  present, 
only  brownish  amorphous  globules  or  yellow  scales  are 
found  in  the  deposit.  By  performing  the  test  in  this  simple 
manner  Williamson  ha-s  never  obtained  any  ciystals  of 
phenylglucosazone  in  normal  urine. 

Much  discussion  has  arisen  concerning  the  proper  method  of 
performing  this  test  for  sugar.  According  to  Hirschl,^  if  a  mix- 
ture be  left  on  a  water-bath  for  a  shorter  time  than  one  hour,  a 
glycuronic  acid  compound  (melting-point,  150°  C.)  is  formed, 
which  is  liable  to  be  mistaken  for  phenylglucosazone.  On  the 
other  hand,  it  has  been  pointed  out  by  a  number  of  observers 
that  if  the  mixture  be  kept  on  a  water-bath  for  as  long  a  period 
as  one  hour,  a  small  deposit  of  the  crystals  may  be  obtained  in 
many  normal  urines.  These  crystals  are  frequently  of  a  doubt- 
ful nature,  even  after  they  have  been  dissolved  in  hot  alcohol 
andrecrystallized. 

According  to  Fisher,  the  reaction  which  takes  place  be- 
tween phenylhydrazin  and  glucose  is  represented  by  the 
following  equation  : 

CeHpPe  +  2CeH5  .  N2H3  =  CiaH^.N^O,  +  2H,0  +  2H. 

A  great  advantage  of  the  phenylhydrazin  test  for  sugar 
is  that  it  gives  no  reaction  with  uric  acid,  kreatinin,  hip- 
puric  acid,  pyrocatechin,  etc.,  while  wath  Fehling's  test,  as 
ordinarily  applied  (boiling  the  urine  and  F"ehling's  solution 
together),  these  substances  are  often  a  source  of  fallacy. 

Plicnylglucosazone  (C^H.^N^O^)  cr>'stallizes  in  bright,  fine, 
yellow  needles  (see  Plate  4),  which  are  arranged  singly 
or  in  stellate  groups.      They  are  almost  insoluble  in  water, 

1  "  Zeitschr.  f.  physiol.  Ch.,"  xiv,  377. 


152  ABNORMAL  CONSTITUENTS  OF  URINE. 

but   dissolve   in    boiling    alcohol,   and    melt    at     204°  to 
205°  C. 

Fermentation  Test. — The  fermentation  test  is  an  excel- 
lent and  reliable  one  for  the  detection  of  sugar  (glucose)  in 
all  cases  in  which  the  urine  contains  more  than  ^  of  i 
per  cent,  of  sugar.  The  test  depends  upon  the  fermenta- 
tion of  the  sugar  by  means  of  yeast,  yielding  alcohol,  car- 
bon dioxide,  and  various  other  less  important  substances, 
vi'ith  a  resulting  decrease  in  the  specific  gravity.  The  fol- 
lowing equation  represents  the  reaction  which  takes  place  : 

C6H,A  =  2C2H,0  +  2CO,. 

The  most  convenient  method  of  applying  this  test  is  as 
follows  :  Take  a  test-tube,  preferably  one  of  large  diameter, 
introduce  into  it  a  piece  of  compressed  yeast  about  the 
size  of  a  pea,  and  fill  the  test-tube  to  the  top  with  the 
urine  to  be  tested.  Stopper  tightly  with  a  rubber  cork 
having  a  single  perforation,  through  which  a  glass  tube  is 
passed  so  that  it  reaches  nearly  to  the  bottom  of  the  test- 
tube.  Above  the  cork  the  glass  tube  is  bent  at  right 
angles  to  the  perpendicular  of  the  test-tube,  and  some  four 
inches  from  this  bend  the  tube  is  again  given  a  right- 
angled  bend  downward.  A  receptacle  is  then  placed 
under  the  end  of  the  glass  tube. 

If  sugar  is  present,  evidences  of  fermentation  will  pre- 
sent themselves,  generally  within  twelve  hours,  by  the  for- 
mation of  carbon  dioxide  which  rises  to  the  surface  of  the 
urine,  but,  being  held  in  by  the  cork,  forces  the  urine  out 
through  the  bent  glass  tube  into  the  receptacle  at  the  end 
of  the  tube.  Sufficient  carbonic  acid  gas  is  usually  obtained 
from  highly  saccharine  urines  to  force  out  all  of  the  urine 
in  the  test-tube.  The  test  should  be  subjected  to  a  tem- 
perature of  80°  to  90°  F. 

This  test  can  not  be  relied  upon  if  less  than  j^  per  cent, 
of  sugar  is  present,  since  a  small  quantity  of  carbon  dioxide 
is  likely  to  be  absorbed  by  the  urine  (water  will  absorb  an 
equal  volume  of  carbonic  acid  gas). 

In  the  performance  of  this  test  it  should  be  borne  in 
mind  that  some  specimens  of  yeast  spontaneously  evolve 
gas,  and  it  is,  therefore,  best  to  perform  with  each  urine 
tested  a  control  experiment  with  yeast  mixed  with  water 
instead  of  urine,  in  order  to  judge  of  the  amount  of  gas  in 
the  yeast  itself. 


GLUCOSE.  153 

The  chief  disadvantage  of  the  fermentation  test  is  that  it 
requires  several  hours  for  its  completion,  and  it  is  therefore 
not  practical  for  routine  work. 

Bismuth  Tests. — These  tests  depend  upon  the  power 
that  sugar  (glucose)  possesses  of  reducing  the  salts  of 
bismuth,  with  a  resulting  black  precipitate  of  metallic 
bismuth. 

(a)  Botiger's  Test. — Take  one-fourth  of  a  test-tube  of  the 
suspected  urine,  add  an  equal  volume  of  potassic  hydrate 
(liquor  potassae,  U.  S.  P.),  or  a  solution  of  sodic  carbonate 
(i  part  of  crystals  to  3  parts  of  distilled  water),  mix,  and 
add  a  small  amount  of  subnitrate  of  bismuth.  Shake,  and 
boil  the  whole  mixture,  and  if  sugar  be  present,  a  black 
precipitate  appears,  which  clings  to  the  sides  of  the  test- 
tube.  A  gray,  instead  of  a  black,  precipitate  is  obtained  if 
the  quantity  of  sugar  is  small,  in  which  case  a  smaller 
amount  of  bismuth  should  be  used  in  making  the  test. 
According  to  Tyson,  this  gray  precipitate,  said  to  be  char- 
acteristic of  small  quantities  of  glucose,  sometimes  presents 
itself  when  no  sugar  is  present. 

The  urine  to  be  tested  should  be  free  from  albumin  and 
other  substances  containing  sulphur,  since  traces  of  sulphur 
combine  with  the  bismuth  salts  to  form  bismuth  sulphide, 
which  is  likely  to  be  mistaken  for  metallic  bismuth.  To 
obviate  this  difficulty,  Brijcke  has  suggested  the  following  : 

{6)  Bruckc's  Alodification  of  Bottgcr' s  Test. — Frohn's 
reagent  ^  is  recommended  for  the  removal  of  the  sulphur 
compounds  in  the  following  way  :  Pour  into  a  test-tube  a 
certain  quantity  of  water,  say  10  c.c,  and  fill  another  tube 
to  the  same  level  with  the  suspected  urine.  To  the  first 
add  a  drop  of  Frohn's  reagent,  which  will  cause  a  pre- 
cipitate. Then  add,  drop  by  drop,  concentrated  hydro- 
chloric acid  until  the  precipitate  is  redissolved.  In  this 
way  the  approximate  quantity  to  be  added  to  the  suspected 
urine  is  ascertained.  Acidulate  the  urine  in  the  other  test- 
tube  with  the  same  quantity  of  hydrochloric  acid  ;  treat  it 
with  the  reagent  until  precipitation  is  complete,  and  filter. 
The  filtrate,  which  should  not  be  rendered  turbid  on  the 
further  addition  of  hydrochloric  acid  or  the  reagent,  is 
thoroughly   boiled   with   an    excess   of  sodic    or    potassic 

1  Frohn's  reagent :  1. 5  grams  of  freshly  precipitated  bismuth  subnitrate  are 
mixed  with  20  grams  of  water,  and  heated  to  boiling  ;  then  7  grams  of  potas- 
sium iodide  and  20  drops  of  concentrated  hydrochloric  acid  are  added. 


154  ABNORMAL  CONSTITUENTS  OF  URINE. 

hydrate,  as  in  Bottger's  test.  If  a  gray  or  black  precipitate 
or  color  is  formed,  sugar  is  present.  Brucke  claims  that 
this  test  will  detect  0.4  per  cent,  of  glucose  in  water. 

(r)  Ny lander's  Test. — Almen's  fluid  is  used.  It  consists 
of  4  grams  of  Rochelle  salt  (sodio-potassic  tartrate),  dis- 
solved in  100  c.c.  of  a  10  per  cent,  solution  of  caustic  soda. 
The  fluid  is  warmed,  and  2  grams  of  subnitrate  of  bismuth 
are  added.  One  volume  of  this  fluid  is  added  to  10  volumes 
of  urine,  and  the  mixture  heated.  In  a  few  minutes  (three 
to  five)  it  will  become  black  if  sugar  be  present.  The  reac- 
tion will  indicate  the  presence  of  at  least  o.  i  per  cent,  of 
sugar.  This  test  is  not  applicable  to  albuminous  urines,  and 
the  reaction  occurs  in  the  presence  of  melanin  or  melanogen, 
or  when  the  fluid  is  rich  in  reducing  substances  other  than 
sugar. 

Methylene-blue  Test. — Methylene-blue  is  decolorized 
by  glucose  in  a  warm  alkaline  solution.  In  performing 
the  test  the  diabetic  or  suspected  urine  is  diluted  (i  part  to 
9  of  water).  Of  this  diluted  urine  2  c.c.  are  mixed  with 
6  c.c.  of  a  I  :  3000  solution  of  methylene-blue,  and  2  c.c. 
of  potassic  hydrate  are  then  added.  The  mixture  is  boiled 
for  one  or  two  minutes,  when  the  blue  color  disappears  if 
sugar  be  present.  Care  must  be  taken  that  the  fluid  is 
shaken  as  little  as  possible,  since  the  blue  color  returns 
easily,  owing  to  the  action  of  the  oxygen  in  the  air.  It  is 
important  to  dilute  the  urine,  as  all  undihitcd  urine  dis- 
charges the  blue  color ;  but  normal  urine  diluted  i  :  9  of 
water  does  not  decolorize  methylene-blue. 

Williamson  has  found  that  a  distinct  reaction  is  obtain- 
able by  this  method  when  diabetic  urine  is  diluted  until  the 
percentage  of  sugar  is  only  0.07,  but  when  further  diluted, 
until  it  is  0.014,  "o  reaction  is  obtained.  Urines  rich  in 
urates  give  a  doubtful  reaction  when  diluted  i  :  9.  Since 
urine  often  contains  reducing  substances  other  than  sugar, 
Frohlich  ^  recommends  that  it  be  treated  first  with  5  c.c. 
of  a  concentrated  solution  of  lead  acetate,  and  with  5  c.c. 
of  a  solution  of  basic  acetate  of  lead  ;  then  take  an  equal 
quantity  of  the  filtrate  and  a  concentrated  solution  of 
methylene-blue  (i  :  300),  add  potassic  hydrate,  and  boil,  as 
previously  indicated.  This  test  is  not  so  satisfactory  as  the 
phenylhydrazin  or  the  P'ehling  test. 

1  "Centralbl.  f.  inn.  Med.,"  1898,  No.  4. 


GLUCOSE.  155 

Numerous  other  tests  have  been  suggested  for  the  de- 
tection of  sugar  in  urine.  The  following  may  be  men- 
tioned :  Diazobenzolsulphonic  acid  (Penzoldt),  picric  acid 
(Johnson),  sodium  or  potassium  hydrate  and  heat  (Moore), 
acetate  of  lead  and  ammonia  (Rubner),  alpha-naphthol  and 
thymol  (Molisch),  and  indigo-carmine  (Mulder).  Most  of 
the  above-named  tests  are  greatly  inferior  to  those  that 
have  been  described. 

Quantitative  Determination  of  Sugar  in  Urine. — A 
quantitative  determination  of  the  sugar  should  be  made  in 
all  cases  in  which  it  has  been  detected.  It  is  only  by  a 
knowledge  of  the  quantity  of  sugar  present  that  a  diag- 
nosis of  the  condition  can  be  made,  the  severity  of  the  dis- 
ease ascertained,  and  the  results  of  treatment  judged.  The 
twenty-four-hour  quantity  of  urine  should  be  accurately 
kept,  and  while  it  is  being  collected,  put  in  a  cool  place  to 
prevent  fermentation.  The  entire  secretion  for  the  twenty- 
four  hours  should  then  be  thoroughly  mixed  and  measured, 
and  a  sample  of  this  taken  for  the  determination.  The 
urine  obtained  at  a  single  micturition  should  not  be  used 
for  the  quantitative  test,  for  the  reason  that  there  is  consid- 
erable variation  in  the  quantity  of  sugar  eliminated  :  ac- 
cording to  the  time  of  day,  and  the  length  of  time  after  a 
meal. 

The  total  quantity  in  grams  should  in  every  instance  be 
calculated.  A  knowledge  of  the  percentage  of  sugar  alone 
is  never  sufficient,  for  the  percentage  in  itself  means  little  if 
the  total  quantity  is  not  determined.  In  routine  work  the 
percentage  is  usually  obtained,  but  only  for  the  sake  of 
convenience  in  figuring  the  total  number  of  grams  of  sugar. 
'  Fehling's  Test. — This  is  one  of  the  most  practical 
quantitative  tests  for  sugar  in  urine,  and  is  conducted  by 
the  titration  method,  using  the  modified  Fchling  s  solution, 
the  formula  of  which  is  given  on  page  148. 

The  process  depends  upon  the  fact  that  the  blue  color 
disappears,  and  that  the  copper  is  completely  precipitated 
from  a  definite  quantity  of  Fehling's  solution  by  a  given 
amount  of  grape-sugar ;  thus,  every  20  c.c.  of  the  Fehling's 
solution  used  require  50  milligrams  of  sugar  to  completely 
reduce  it. 

Necessary  Apparatus  (Fig.  17). — A  Florence  flask  of 
250  c.c.  capacity  ;  a  common  retort-stand  with  a  burette- 
holder  attachment,  and  with  a  piece  of  copper-  or  iron-wire 


156 


ABNORMAL  CONSTITUENTS  OF  URINE. 


gauze  that  is  large  enough  to  cover  one  of  the  rings  of 
the  stand  (a  tripod,  the  top  of  wjiich  is  covered  with  cop- 
per-wire gauze,  may  be  conveniently  used) ;  a  25-  or  50-c.c. 
burette,  which  is  graduated  to  tenths  of  a  cubic  centimeter ; 
a  lo-c.c.  pipette;  a  loo-c.c.  glass-stoppered  graduate;  and 
a  Bunsen  burner  or  a  large  spirit-lamp. 


0 


Fig.  17. — Apparatus  for  the  quantitative  estimation  of  sugar :  wi,  Meniscus. 


The  analysis  should  be  conducted  as  follows  :  First  take 
the  specific  gravity  of  the  urine  to  be  tested,  then  test  for 
albumin, — preferably  by  the  nitric  acid  test, — and  if  more 
than  a  trace  be  present,  remove  it  according  to  the  directions 
given  on  page  129. 


GLUCOSE.  157 

If  the  specific  gravity  of  the  urine  is  more  than  1030,  dilute 
it  I  :  10  witii  distilled  water  (urine,  i  ;  water,  9) ;  \i  less  than 
1030,  dilute  it  I  :  5  (urine,  i  ;  water,  4).  Mix  thoroughly, 
and  pour  the  diluted  urine  into  the  burette,  filling  it  to  the 
zero  mark,  care  being  taken  to  expel  all  air  from  below  the 
stop-cock.  Next  take  10  c.c.  of  each  of  the  solutions  A 
and  B  by  means  of  the  lO-c.c.  pipette,  and  place  in  the 
250-c.c.  flask.  Add  60  c.c.  of  distilled  water,  making  the 
entire  volume  amount  to  80  c.c.  Place  the  flask  on  the 
wire  gauze,  and  boil  the  mixture.  After  the  diluted  Feh- 
ling's  solution  has  boiled  for  a  short  time, — say  for  two  or 
three  minutes, — and  it  is  found  that  the  solution  does  not 
show  evidences  of  reduction,  the  diluted  urine  is  added, 
drop  by  drop,  from  the  burette  into  the  Fehling's  solution, 
which  is  kept  boiling.  When,  on  removing  the  flame,  after 
a  series  of  observations,  it  is  found  that  the  meniscus  has 
lost  its  blue  color  and  has  become  colorless,  ^  the  reaction 
is  complete. 

The  inenisais  (Fig.  17,  ;//),  which  is  seen  as  a  clear  line 
(blue  at  first  and  later  colorless),  is  best  detected  by  plac- 
ing the  flask  between  the  eye  and  the  light.  As  the  eye  is 
raised  and  lowered,  this  clear  line  will  be  seen  just  beneath 
the  surface  of  the  fluid. 

The  blue  color  having  disappeared  from  the  mixture,  the 
number  of  cubic  centimeters  of  diluted  urine  employed  is 
read  off.  Since  it  takes  just  50  milligrams  (0.050  gram) 
of  sugar  to  completely  reduce  the  cupric  oxide  in  the  20 
c.c.  of  Fehling's  solution  used,  the  percentage  of  sugar  in 
the  urine  may  be  readily  calculated,  and  from  the  per  cent., 
the  number  of  grams  of  sugar  eliminated  in  twenty-four 
h,ours. 

Example :  If  15  c.c.  of  diluted  urine  were  necessary  to 
complete  the  test,  and  the  urine  was  originally  diluted  i  : 
10,  then  15  H-  10=  1.5  c.c.  of  undiluted  urine.  Since  1.5 
c.c.  of  undiluted  urine  reduced  the  copper,  and  50  milli- 
grams of  sugar  accomplish  the  same  end,  then  1.5  c.c.  of 
urine  must  contain  50  milligrams  of  sugar.  The  percent- 
age is  obtained  according  to  the  following  proportion  : 

1.5  :  0.050  :  :  ICO  :  x 
X  ---=  3  yi  per  cent. 

'  When  the  test  solution  is  allowed  to  stand  for  a  short  time  after  the  test  has 
been  completed,  it  again  becomes  blue,  due  to  the  reoxidation  by  the  oxygen 
from  the  air.     This  should  not  be  mistaken  for  an  incomplete  reduction. 


158  ABNORMAL  CONSTITUENTS  OF  URINE. 

Suppose  the  total  quantity  of  urine  in  twenty-four  hours 
amounted  to  2000  c.c,  then  ^^        =  66.6  grams, ^  the 

'  100  O  ' 

quantity  of  sugar  in  twenty-four  hours. 

Precautions :  i.  The  urine  should  be  added  to  the  boil- 
ing Fehling's  solution,  drop  by  drop,  in  order  to  obtain  a 
suboxide  precipitate  that  will  settle  in  a  very  short  time. 
If  a  considerable  quantity  of  the  urine  is  added  at  a  time, 
the  precipitate  will  not  settle  well,  and  the  meniscus  can 
not  be  distinctly  seen. 

2.  A  yellow  color  to  the  meniscus  or  to  the  body  of 
the  solution,  besides  that  produced  by  the  suboxide  pre- 
cipitate, indicates  that  too  much  of  the  saccharine  urine 
has  been  added,  and  that  the  end  reaction  has  passed.  A 
new  titration  is  then  necessary. 

3.  The  Fehling's  solution  should  be  kept  at  the  boiling 
temperature,  except  during  the  time  required  for  observing 
the  meniscus.  As  soon  as  the  solution  cools,  reoxidization 
of  the  copper  begins,  and  consequently  the  blue  color 
reappears. 

Purdy's  Method. — The  following  modification  of  Feh- 
ling's method  is  advised  by  Dr.  Purdy,  who  claims  that  by 
the  use  of  his  solution  various  defects  of  Fehling's  method 
are  overcome  : 

Take  of  pure  cupric  sulphate,  4.752  grams;  potassium 
hydroxide,  23.5  grams  ;  strong  ammonia  (U.  S.  P. — specific 
gravity  0.9)  350  c.c.  ;  glycerine  (C.P.),  38  c.c.  ;  distilled 
water,  to  make  lOOO  c.c. 

Prepare  by  dissolving  the  cupric  sulphate  and  glycerine 
in  200  c.c.  of  distilled  water  with  the  aid  of  gentle  heat. 
In  another  200  c.c.  of  distilled  water  dissolve  the  potassium 
hydrate,  mix  the  two  solutions,  and,  when  cool,  add  the 
ammonia.  Finally,  with  distilled  water  bring  the  volume 
of  the  whole  to  exactly  lOOO  c.c.  Thirty-five  cubic  centi- 
meters of  this  solution  are  reduced,  upon  boiling,  by 
exactly  2  centigrams  (0.02  gram)  of  grape-sugar. 

Proceed  by  accurately  measuring  35  c.c.  of  the  solution 
into  the  flask,  dilute   with   about   two   volumes  of  distilled 

'  .Since  this  iiielluxl  of  lii;uring  is  based  on  the  supposition  tlmt  i  c.c.  is 
equal  to  i  gram,  the  same  as  distilled  water,  it  can  not  rightly  be  applied  to 
urine,  l  c.c.  of  which  weighs  more  than  I  c.c.  of  distilled  water  ;  therefore,  the 
figures  66.6  represent  only  the  approximate  quantity  of  sugar.  Accurate  figures 
may  be  obtained  by  correcting  for  the  difference  between  the  specific  gravity 
of  the  urine  tested  and  that  of  distilled  water. 


GLUCOSE.  159 

water,  and  bring  the  whole  thoroughly  to  the  boiling-point. 
Fill  the  burette  to  the  zero  mark  with  the  urine  to  be  tested, 
and  slowly  discharge  the  urine  into  the  boiling  test  solution, 
drop  by  drop,  until  the  blue  color  begins  to  fade  ;  then, 
still  more  slowly,  three  to  five  seconds  elapsing  after  each 
drop,  until  the  blue  color  completely  disappears  and  the 
test  solution  is  left  perfectly  colorless  and  transparent.  The 
number  of  cubic  centimeters  required  to  discharge  the  blue 
color  in  35  c.c.  of  the  test  solution  contains  exactly  2  centi- 
grams (0.02  gram)  of  sugar. 

If  35  c.c.  of  the  test  solution  are  reduced  by  2  c.c.  of 
urine,  then  i  :  0.02  :  :  100  :  x,  and  x  =  i  per  cent,  of 
sugar;  reduced  by  i  c.c,  2  per  cent.;  reduced  by  ^  of  a 
cubic  centimeter,  3  per  cent.  ;  reduced  by  ^  of  a  cubic 
centimeter,  4  per  cent.  ;  reduced  by  ^  of  a  cubic  centimeter, 
8  per  cent. 

If  absolute  accuracy  of  results  is  desired,  it  is  better  to 
dilute  the  urine  to  be  tested  with  2  volumes  of  distilled 
water,  and  divide  the  product  by  3  ;  especially  if  the  per- 
centage of  sugar  is  high. 

The  advantages  claimed  by  Purdy  for  this  test  are  (i) 
its  perfect  end-reaction  ;  (2)  the  stability  of  the  solution  ; 
(3)  its  rapidity  of  application,  only  requiring  about  five 
minutes,  and  (4)  its  accuracy. 

Fermentation  Test. — The  fermentation  test  for  sugar 
can  not  be  considered  an  accurate  quantitative  test,  although 
it  may  be  used  with  advantage  for  determining  the  approxi- 
mate quantity  of  sugar  present.  The  method  suggested  by 
Roberts  is  as  follows  :  Four  ounces  of  the  saccharine 
urine  are  placed  in  a  twelve-ounce  bottle,  and  a  piece  of 
cornpressed  yeast  is  added.  The  bottle  is  then  stoppered 
with  a  nicked  cork  to  permit  the  escape  of  the  carbonic  acid 
gas,  and  set  aside  in  a  warm  place  to  ferment.  Beside  it 
is  placed  a  tightly  corked  four-ounce  bottle  filled  with  the 
same  urine,  but  without  any  yeast.  In  from  eighteen  to 
twenty-four  hours  fermentation  will  have  ceased.  The  fer- 
mented urine  is  then  decanted  into  a  urinometer-glass,  and 
the  specific  gravity  taken.  The  specific  gravity  of  the  un- 
fermented  urine  in  the  other  bottle  is  taken  at  the  same 
time,  and  the  loss  of  density  ascertained.  Roberts  has 
shown  that  every  degree  in  the  specific  gravity  lost  in 
fermentation  corresponds  approximately  to  ojie  grain  of 
sugar  per  Jluidounce.       Thus,    if  before    fermentation    the 


IGO  ABNORMAL  CONSTITUKNTS  OF  URINE. 

specific  gravity  was  1040  and  after  feriiientation  it  is 
1020,  it  will  have  contained  20  grains  of  sugar  to  the 
fluidounce  of  urine.  The  two  portions  of  urine  in  the 
bottles  should  be  subjected  to  exactly  the  same  tempera- 
ture. 

The  percentage  of  sugar  may  be  roughly  ascertained  by 
multiplying  the  number  of  degrees  lost  in  the  specific  grav- 
ity by  the  arbitrary  coefficient  0.23. 

In  the  hands  of  the  writer  the  fermentation  test  yields 
results  which  are  in  the  neighborhood  of  one-half  per  cent, 
below  those  obtained  by  using  Fehling's  solution.  A 
decided  objection  to  this  method  is  that  it  requires  from 
eighteen  to  twenty-four  hours  for  the  completion  of  the 
analysis. 

Einhorn  has  devised  a  fermentation  apparatus  that 
gives  only  approximate  results.  Two  specially  con- 
structed and  graduated  tubes  are  used,  one  of  which  is 
filled  with  a  mixture  of  the  suspected  urine  and  a  small 
quantity  of  yeast,  and  the  other  with  a  mixture  of  normal 
urine  and  yeast,  as  a  control.  The  tubes  are  then  set  aside 
at  a  temperature  of  from  30°-34°  C.  (86°-93°  F.),  and  left 
until  fermentation  has  ceased.  The  percentage  of  sugar  is 
then  read  off  from  the  column  of  carbon  dioxide  present. 
If  the  second  tube  also  shows  a  small  amount  of  gas,  the 
figure  corresponding  to  the  amount  is  deducted  from  the 
reading  in  the  first  tube. 

By  Polarization. — Glucose,  or  grape-sugar,  rotates  the 
plane  of  polarized  light  toward  the  right,  and  upon  this 
fact  a  quantitative  test  for  that  substance  is  based. 
Although  a  quantitative  deterniination  of  grape-sugar  by 
this  method  is  theoretically  accurate,  when  applied  to  urine 
it  is  open  to  fallacy,  since  the  urine  is  apt  to  contain  other 
substances  such  as  laivulose,  ;5-oxybutyric  acid,  etc.,  which 
rotate  the  plane  of  polarized  light  in  the  opposite  direction. 
As  pointed  out  by  v.  Jaksch,  Hoppe-Seyler,  and  others,  it 
is  advisable  to  apply  the  test  both  before  and  after  fermen- 
tation, and  the  difference  in  the  results  w'ill  represent  the 
quantity  of  grape-sugar  in  solution. 

A  large  variety  of  polariscopes  have  been  constructed 
for  this  purpose,  among  the  best  of  which  are  those  of 
Soleil,  Laurent,  Lippich,  Ultzmann,  Misterlich,  v.  Fleischl, 
and  Schmidt  &  Haensch.  In  recent  years  the  use  of  the 
half-shadow  polariscope  has  rendered  this  quantitative  test 


GLUCOSE. 


161 


more  reliable,  on  account  of  the  accuracy  with  which  the 
extent  of  rotation  is  determined. 

The  polariscope  manufactured  by  Schmidt  &  Haensch, 
of  Berlin,  is  one  of  the  best.  ^  It  is  a  half-shadow  instru- 
ment, being  so  made  that  gas  or  petroleum  light  can  be 
used  instead  of  a  sodium  light.  It  determines  direct  per- 
centages of  sugar,  and  is  not  only  accurate,  but  its  operation 
is  quick  and  simple. 


Fig.  i8. — The  Schmidt  &  Haensch  polariscope. 


In  the  Schmidt  &  Haensch  apparatus,  as  represented  in 
figure  1 8,  O  is  the  ocular ;  S,  the  ivory  scale  with  vernier  ; 
L,  the  ocular  by  means  of  which  the  scale  is  read  ;  K,  the 
screw-head  by  which  the  quartz  wedge  is  moved  ;  B,  the 
glass  tube  for  holding  the  suspected  fluid ;  and  P,  the 
receptacle  for  the  glass  tube. 

1  This  instrument  can  be  obtained  of  Messrs.  Eimer  &  Amend,    205-211 
Third  Avenue,  New  York  city. 
II 


162  ABNORMAL  CONSTITUENTS  OF  URINE. 

The  source  of  light  is  a  well-constructed  lamp,  with  a 
flat  burner,  for  either  gas  or  petroleum  ;  a  special  lamp  can 
be  constructed  so  as  to  use  electric  light.  The  lamp  should 
be  removed  about  30  cm.  from  the  apparatus,  and  so 
adjusted  that  the  illuminating  lens  in  the  chimney  of  the 
lamp  shall  be  exactly  central  to  the  optical  axis  of  the 
apparatus.  In  looking  through  the  instrument  a  clear 
circular  field  should  be  seen,  with  a  sharp  perpendicular 
line  between  the  two  halves  of  the  field.  If  the  field  is  not 
perfectly  distinct,  the  ocular  (O)  should  be  drawn  out  until 
the  perpendicular  line  and  the  circular  outline  of  the  field  are 
sharply  defined.  This  adjustment  should  be  made  without 
the  glass  tube — that  is,  the  receptacle  should  be  empty  and 
its  cover  closed. 

The  delicate  scale  (/^),  on  which  are  found  numbers  cor- 
responding to  the  principal  lines,  is  read  through  the 
ocular  (L).  The  zero  point  on  the  vernier  (5)  should  be  made 
to  correspond  exactly  with  that  on  the  scale  (F)  by  means 
of  the  adjustment-screw  (AT).  When  the  zero  point  on  the 
vernier  is   opposite   that  on  the  scale,  the  two  halves  of 

the  field  of  the  apparatus 
should  exactly  correspond — 
that  is,  they  should  be  equally 
lighted.  (See  ^,  Fig.  19.)  If, 
however,  the  two  halves  of 
the  field  should  not  receive 
an  equal  amount  of  light, 
they  should  be  made  to  correspond  exactly  by  the  use  of  the 
adjustment-screw  {-fC).  The  vernier  (S)  is  then  moved  to 
the  side  corresponding  by  means  of  a  micrometer-screw, 
until  its  zero  point  is  opposite  that  on  the  scale  (F). 

Having  adjusted  the  apparatus,  the  glass  tube  is  then 
filled  with  the  suspected  urine,  and  placed  in  the  receptacle. 
The  two  halves  of  the  field,  which  are  then  found  to 
receive  an  7/ ncqua/  amount  of  light,  are  made  to  correspond 
by  means  of  the  adjustment-screw  (A'),  and  the  rotation  to 
the  right  or  to  the  left  read  on  the  scale.  The  result  is  the 
percentage  of  sugar  in  the  fluid.  Every  interval  on  the 
scale  corresponds  to  ^  per  cent.,  and  between  these  inter- 
vals are  lines  which  are  equivalent  to  -^-^  per  cent. 

Example. — If  the  scale  is  moved  toward  the  left,  the 
number  of  scale  intervals  that  have  been  passed  is  reckoned 
from  the   zero  point   on   the   vernier.      Suppose    that  the 


GLUCOSE.  163 

number  of  scale-intervals  passed  is  7,  and  that  the  zero 
point  of  the  vernier  stands  between  7  and  8  and  at  the 
mark  corresponding  to  0.3  per  cent.,  then 

7  half  per  cent.  =  3.5  -|-  0.3  =  3.8  per  cent. 

A  similar  reading  is  made  when  the  scale  is  moved 
toward  the  right.  In  order  to  read  direct  percentages  of 
sugar  on  the  scale  the  200-mm.  tube  should  always  be 
used.  If  it  should  be  necessary,  on  account  of  the  turbidity 
of  the  urine,  to  use  the  100-  or  50-mm.  tubes,  the  reading 
in  every  instance  should  be  multiplied  by  either  2  ( loo-mm. 
tube)  or  4  (50-mm.  tube). 

Grape-sugar  rotates  the  plane  of  polarized  light  toward 
the  right ;  albumin  rotates  toward  the  left.  Consequently, 
in  a  urine  containing  both  albumin  and  sugar  the  degi'ee 
of  rotation  to  the  right  or  to  the  left  will  depend  upon  the 
predominance  of  one  or  the  other  of  these  substances. 

Prccautio)is. — The  urine  must  be  clear  ;  if  it  is  turbid,  it 
should  be  filtered  as  rapidly  as  possible  through  a  plaited 
filter  of  soft  filter-paper.  If  the  urine  is  then  so  highly 
colored  that  when  the  long  glass  observation  tube  (200 
mm.)  is  used  the  line  of  separation  between  the  two  halves 
of  the  field  can  not  be  distinctly  seen,  the  shorter  glass 
observation  tube  (100  or  50  mm.)  should  be  used.  If  the 
field  is  still  indistinct,  the  urine  should  be  shaken  in  a  flask 
with  pure,  dry,  animal  charcoal,  or  decolorized  by  add- 
ing to  the  urine  one-tenth  of  its  volume  of  basic  acetate  of 
lead,  and  then  filtered.  In  the  latter  instance  the  results 
obtained  by  polarization  must  be  multiplied  by  ■^,  on 
account  of  the  dilution. 

The  temperature  of  the  urine  must  be  from  15°  to  20°  C. 
If  the  urine  is  free  from  albumin,  the  percentage  of  sugar  is 
obtained  directly  by  the  use  of  the  200-mm.  tube,  in  the 
manner  mentioned.  If,  on  the  other  hand,  the  urine  con- 
tains albumin,  a  second  polarization  is  necessary  after  the 
removal  of  the  albumin.  The  albumin  is  removed  as  fol- 
lows :  Take  100  c.c.  of  the  urine  in  an  evaporating  dish, 
and  place  on  a  water-bath.  Add  acetic  acid,  drop  by  drop, 
continuing  the  heat  until  a  flocculent  precipitate  appears. 
Filter  as  quickly  as  possible,  cool,  and  add  sufficient  dis- 
tilled water  to  the  filtrate  to  make  100  c.c.  The  result  of 
the  second  polarization  will  represent  the  exact  percentage 
of  sugar. 


164  ABNORMAL  CONSTITUENTS  OF  URINE. 

LACTOSE. 

(MiLK-SUCAR.) 

Lactose,  C,2H220ii'  ^^  ""^  infrequently  found  in  small 
amounts  in  the  urine  of  women  (the  maximum  being  about 
one  per  cent.)  near  the  end  of  gestation,  but  more  especially 
in  nursing  women  in  whom  the  flow  of  milk  has  become 
impeded,  as  in  cases  of  mastitis.  Lactose  is  also  frequently 
seen  in  the  urine  of  women  who  have  weaned  their  children. 
Its  presence  may  continue  for  from  three  to  four  days,  and 
even  a  week,  particularly  in  those  in  whom  the  secretion 
of  milk  is  copious.  Whereas  lactose,  when  present,  is  an 
abnormal  constituent  of  the  urine,  its  presence  can  not  be 
considered  of  pathologic  significance.  Its  chief  importance 
lies  in  the  fact  that  it  should,  in  all  cases,  be  distinguished 
from  glucose. 

Lactose  crystallizes  in  colorless,  four-sided  prisms,  with 
acuminated  ends,  bounded  by  four  angles.  The  specific 
rotary  power  of  lactose  is  -|-  52.5°,  and  is  independent  of 
the  concentration  in  solutions  that  contain  up  to  56  per 
cent,  at  ordinary  temperatures.  It  reduces  the  salts  of 
copper  upon  boiling  in  alkaline  solution,  but  more  feebly 
than  grape-sugar.  It  does  not  undergo  alcoholic  fermenta- 
tion with  yeast ;  is  quite  soluble  in  cold,  and  freely  soluble 
in  hot,  water  ;  insoluble  in  alcohol  and  ether.  It  is  pre- 
cipitated by  acetate  of  lead  and  ammonia  (Briicke). 

Isolation. — According  to  F.  Hofmeister,  the  following 
process  serves  for  the  isolation  of  milk-sugar  :  Since  evapo- 
ration of  the  urine  is  liable  to  decompose  the  lactose,  it  is 
directly  precipitated  by  a  solution  of  acetate  of  lead  and 
ammonia,  and  the  precipitate  is  washed.  The  filtrate  and 
wash-water  should  again  be  precipitated  with  lead  acetate 
and  ammonia,  and  the  process  repeated  until  the  filtrate 
shows  no  more  rotation.  The  washed  precipitate  is  then 
suspended  in  cold  water,  and  decomposed  with  sulphureted 
hydrogen.  The  solution  is  freed  from  the  greater  part  of 
the  hydrochloric  acid  by  shaking  with  silver  oxide,  and 
from  the  remainder  of  the  HCl  by  neutralizing  the  filtrate. 
The  solution  is  once  more  treated  with  H.,S,  and  the  mix- 
ture evaporated  after  the  addition  of  barium  carbonate.  Be- 
fore the  residue  becomes  syrupy  it  should  be  treated  with  a 
sufficient  amount  of  90  per  cent,  alcohol  to  produce  a 
flocculent,  rapidly  settling  precipitate.      The  filtrate,  placed 


LEVULOSE.  165 

in  a  desiccator,  yields  cr>'stals  of  lactose,  which  should  be 
washed  with  dilute  alcohol,  then  recrystallized  from  water 
after  decolorizing  with  animal  charcoal,  and  finally  freed 
from  adhering  substances  by  boiling  with  60  to  70  per  cent, 
alcohol.  These  crystals  are  then  subjected  to  the  tests 
for  lactose,  including  that  with  Barfoed's  reagent. 

Detection. — If  the  urine  reduces  Fehling's  solution 
feebly,  does  not  ferment  with  yeast,  and  rotates  the  polar- 
ized light  strongly  to  the  right,  lactose  is  probably  present, 
especially  if  the  urine  is  that  of  a  pregnant  or  nursing 
woman.  A  confirmatory  test  may  be  made  by  using  the 
phenylhydrazin  test,  which,  in  the  presence  of  lactose,  forms 
an  osazone.  Phenyl-lactosazone  crystallizes  in  the  form  of 
yellow  needles,  which  are  usually  aggregated  in  clusters, 
and  melts  at  200°  C,  with  the  evolution  of  gas.  Lactose,' 
unlike  glucose,  does  not  reduce  Barfoed's  reagent,  1  but 
this  test  can  not  be  applied  to  urine,  since  Barfoed's  re- 
agent is  reduced  to  a  slight  extent  by  normal  urine. 

The  certain  detection  of  lactose  is  secured  only  by  iso- 
lating it  from  the  urine. 

LEVULOSE. 

(Fruit  Sugar.) 

Levulose,  C,.Hj,0^,  is  only  rarely  found  to  be  a  con- 
stituent of  the  urine.  When  present,  it  is  usually  found 
associated  with  grape-sugar,  and  is  rarely,  if  ever,  found 
alone.  In  such  instances  it  usually  happens  that  consider- 
ably more  sugar  is  found  in  diabetic  urine  by  titration  than 
by  polarization,  thus  showing  the  presence  of  a  substance 
that  rotates  to  the  left.  The  diminution  in  the  optical 
activity  of  the  urine  is  not  necessarily  caused  by  a  sugar 
that  rotates  to  the  left,  but  may  be  produced  in  the  absence 
of  albuminous  substances  (albumin,  globulin,  albumose, 
and  peptone)  by  other  bodies,  especially  /5-oxybutyric  acid, 
glycuronic  acid,  cystin,  and  other  compounds. 

It  is  characterized  by  being  noncrystallizable  when 
impure  (although  it  crystallizes  in  long,  wavy  needles 
when  pure),  and  by  turning  the  plane  of  polarized  light  to 

1  Barfoed's  Reagent:  Dissolve  one  part  of  cupric  acetate  in  15  parts  of 
water;  to  200  c.c.  of  this  solution  add  5  c.c.  of  acetic  acid  containing  38  per 
cent,   of  glacial  acetic  acid  ("Journ.   f.  prakt.   Chem."  [2],  Bd.  vi  (1872) 
S.  344)-  \     /    /' 


166  ABNORMAL  CONSTITUENTS  OF  URINE. 

the  left  instead  of  to  the  right.  Its  rotary  power  dimin- 
ishes as  the  temperature  rises,  while  that  of  grape-sugar 
is  independent  of  the  temperature.  Levulose  reduces  the 
salts  of  copper,  although  much  more  feebly  than  grape- 
sugar. 

There  is  no  sure  process  known  for  the  isolation  of 
levulose. 

Detection. — Levulose  is  best  detected  by  means  of  the 
polariscope,  since  it  rotates  the  plane  of  polarized  light  to 
the  left.  It  yields  with  phenylhydrazin  an  osazone  (phenyl- 
levulosazone)  that  crystallizes  in  yellow  needles  whose 
melting-point  is  150°  C,  while  those  formed  from  grape- 
sugar  have  a  melting-point  of  204°  C. 

If  the  left-handed  rotation  is  caused  by  substances  other 
than  levulose,  by  subjecting  the  urine  to  alcoholic  fermen- 
tation the  left-handed  rotation  disappears  if  due  to  this  form 
of  sugar,  and  persists  if  caused  by  other  bodies. 


LAIOSE. 

(Leo's  Sug.a.r.) 

Laiose,  CgHj^Og,  was  first  discovered  by  Leo,^  who  found 
it  in  the  urine  of  3  out  of  21  severe  cases  of  diabetes  mellitus. 
These  urines  gave  1.2  to  1.8  per  cent,  more  sugar  by  titration 
than  by  polarization.  This  sugar  could  not  be  isolated  from  20 
liters  of  normal  urine. 

Laiose  is  closely  allied  to  levulose  in  that  it  rotates  the  plane 
of  polarized  light  to  the  left,  reduces  alkaline  solutions  of  the 
cupric  salts,  and  combines  with  phenylhydrazin.  It  is  not  fer- 
mentable and  does  not  have  a  sweet  taste.  The  neutral  pale- 
yellow  syrup  does  not  crystallize  if  kept  for  a  year.  It  is 
readily  soluble  in  water,  moderately  in  methyl  alcohol,  spar- 
ingly in  ethyl  alcohol,  and  insoluble  in  ether  and  chloroform. 
It  is  completely  precipitated  by  basic  acetate  of  lead  and 
ammonia. 

Isolation. — The  urine  is  precipitated  with  basic  acetate  of 
lead,  and  the  filtrate  with  ammonia.  The  second  precipitate 
contains  the  laiose  together  with  the  dextrose.  The  precipitate 
is  washed  and  decomposed  with  sulphureted  hydrogen.  Since 
the  filtered  fluid  becomes  dark  by  evaporating  in  the  air,  Leo 
concentrated  it  by  distilling  in  a  vacuum,  and  finally  drying 
over  sulphuric  acid.  The  syrupy  residue  is  then  dissolved  in 
methyl  alcohol,  and  the  grape-sugar  that  has  dissolved  with  it  is 

1  Han.s  Leo,  "  Virchow's  Archiv,"  cvn,  108,  1887. 


INOSITE.  167 

precipitated  by  a  solution  of  baryta  in  metliyl  alcohol,  sufficient 
to  give  a  strongly  alkaline  reaction.  It  is  quickly  filtered,  and 
the  filtrate  allowed  to  stand  over  sulphuric  acid  to  remove  the 
ammonia,  by  which  procedure,  besides  the  baric  carbonate,  the 
remainder  of  the  barium  compound  of  sugar  is  precipitated. 
Carbonic  acid  gas  is  passed  through  the  filtrate  to  remove  the 
excess  of  baryta,  and  the  methyl  alcohol  is  distilled  off  in  a 
vacuum,  the  residue  dissolved  in  water,  and  the  baryta  in  solu- 
tion precipitated  by  sulphuric  acid. 

Detection. — Urines  that  do  not  contain  any  more  sugar  by 
titration  than  by  polarization  need  not  be  tested  for  this  form 
of  sugar.  If  the  isolated  substance  is  a  reducing  body,  it  is 
probably  laiose. 


SUBSTANCES  ALLIED  TO  SUGAR. 

INOSITE. 

(Muscle  Sugar.) 

Inosite,  CgH^p^  +  2U.p,  is  a  rare  constituent  of  the 
urine.  It  has  occasionally  been  found  in  small  quantity  in 
diabetes  mellitus,  as  an  accompaniment  of  grape-sugar  ;  in 
the  last  stages  of  certain  forms  of  chronic  disease,  particu- 
larly subacute  glomerular  and  chronic  diffuse  nephritis  ; 
and  also  after  the  ingestion  of  large  quantities  of  water 
(Kulz).  It  has  also  been  found  in  phthisis,  syphilis,  and 
typhus  fever. 

According  to  Neubauer  and  Vogel,  inosite  is  not  a 
sugar ;  but  from  the  experiments  of  Maquenne  i  it  should 
be  grouped  among  the  compounds  of  the  fat  series,  mannite. 

Inosite  forms  in  cauliflower  groups  of  crystals,  and,  at 
times,  in  single  crystals  that  are  three  or  four  lines  in  length. 
It  has  a  sweet  taste,  dissolves  in  7. 5  volumes  of  cold  water 
at  17°  to  20°  C,  readily  in  hot  water,  and  is  slightly  sol- 
uble in  alcohol.  It  is  very  .soluble  in  dilute  or  concen- 
trated acetic  acid,  and  crystallizes  more  readily  from  these 
solutions  than  from  water  (Maquenne).  It  is  insoluble  in 
absolute  alcohol  and  in  ether.  Its  solutions  are  optically 
inactive,  and  it  does  not  combine  with  phenylhydrazin,  and 
is  not  fermentable  by  yeast  ;  it,  however,  undergoes  lactic- 
and  butyric-acid  fermentation.  Inosite  does  not  reduce  the 
cupric    salts  when    boiled    in  the  presence  of  an  alkaline 

1  "  Bull,  dela  Soc.  Chim."  [2],  xi.vii,  290;  XLvni,  58,  1887  ;  "  Comptes 
Rendus,"  civ,  225,  297,  and  1719. 


168  ABNORMAL  CONSTITUENTS  OF  URINE. 

hydrate,  but  not  infrequently  gives  a  greenish  precipitate, 
which  redissolves  on  cooling. 

Isolation. — The  urine  to  be  tested  for  ino.site,  after  any 
albumin  present  has  been  removed,  is  first  concentrated  to 
one-fourth  of  its  bulk,  then  completely  precipitated  with  a 
solution  of  neutral  acetate  of  lead,  avoiding  an  excess,  or 
with  baryta  water,  filtered,  and  the  warmed  filtrate  treated 
with  subacetate  of  lead  as  long  as  any  precipitate  occurs. 
After  twelve  hours  the  subacetate  precipitate  that  contains 
the  inosite,  together  with  lead  oxide,  is  collected  on  a  filter- 
paper,  and  after  washing  is  suspended  in  water  and  decom- 
posed with  sulphureted  hydrogen.  After  standing  a  while 
a  little  uric  acid  first  separates  from  the  filtrate  ;  the  fluid  is 
filtered  from  it,  then  concentrated  as  much  as  possible,  and 
while  boiling  treated  with  three  or  four  times  its  volume  of 
alcohol.  If  a  heavy  precipitate  results  that  rapidly  settles, 
the  hot  alcoholic  solution  is  simply  poured  off,  but  if  a  floc- 
culent  nonadhesive  precipitate  occurs,  the  hot  solution  is 
filtered  through  a  heated  funnel  and  allowed  to  cool.  If, 
after  twenty-four  hours,  groups  of  inosite  crystals  have  de- 
posited, they  are  filtered  and  washed  with  a  little  cold  alco- 
hol. In  this  case  it  is  advisable  to  dissolve  the  precipitate 
once  more  in  as  little  boiling  water  as  possible,  and  precipi- 
tate it  a  second  time  with  three  or  four  volumes  of  alcohol 
in  order  to  avoid  any  loss  of  the  inosite.  If,  however,  no 
crystals  of  inosite  have  separated,  ether  is  gradually  added 
to  the  clear,  cold,  alcoholic  filtrate  until  a  milky  cloudiness 
results  on  shaking  thoroughly,  and  it  is  then  allowed  to 
stand  twenty-four  hours.  Almost  all  of  the  inosite  present  is 
separated  in  the  form  of  shining,  pearly  leaflets  if  too  small 
an  amount  of  ether  has  not  been  used  (an  excess  does  no 
harm).  The  separated  inosite  is  recognized  by  the  reactions 
I  and  2,  given  below. 

Detection. — The  urine  should  be  free  from  albumin. 
The  following  tests  (i  and  2)  depend  upon  the  action  of 
concentrated  nitric  acid  which  oxidizes  inosite  to  rhodizonic 
acid.      The  carbohydrates  do  not  give  these  reactions. 

I.  If  a  fluid  containing  inosite  is  evaporated  in  a  porce- 
lain dish  to  a  few  drops,  and  a  small  drop  of  Millon's 
reagent  ^  is  then  added,  a  yellow  precipitate  is  soon  formed. 

*  Millon's  Reagent :  Dissolve  one  part  of  metallic  mercury  in  two  parts  of 
ordinary  nitric  acid,  evaporate  to  one-half  volume,  and  add  I  ^'^  parts  of  water. 
After  twenty-four  hours  the  clear  supernatant  fluid  is  decanted  from  the  basic  salt. 


GLYCURONIC  ACID.  169 

If  this  is  spread  out  as  much  as  possible  on  the  edge  of  the 
dish  and  again  gently  warmed,  there  remains,  as  soon  as  the 
fluid  is  all  evaporated,  first  a  yellowish  residue,  which 
soon  becomes  red  providing  too  much  of  the  reagent  has 
not  been  added.  The  color  disappears  on  cooling,  but  re- 
appears upon  the  application  of  gentle  heat.  Starch,  lactose, 
mannite,  glycogen,  uric  acid,  urea,  taurin,  and  cystin  do  not 
give  this  red  color ;  albumin  is  colored  red,  and  therefore, 
if  present,  must  be  previously  separated. 

2.  Evaporate  the  fluid  containing  inosite  with  concentrated 
nitric  acid  nearly  to  dryness,  on  a  platinum  dish,  moisten 
the  residue  with  a  few  drops  of  ammonic  hydrate  and  a 
solution  of  calcium  chloride.  Then  evaporate  the  mixture 
to  dryness,  and  there  appears  a  vivid  rose-red  color,  which, 
according  to  Scherer,^  appears  with  even  one  milligram  of 
inosite. 

GLYCURONIC  ACID. 

Glycuronic  acid,  CgHj^jO,,  is  sometimes  found  in  the  urine, 
and  is,  above  all,  most  likely  to  be  mistaken  for  sugar.  It 
probably  occurs  normally  in  very  small  amounts  in  the  urine  as 
cojubined  glycuronic  acid,  coupled  with  potassium  sulphate. 
It  may  appear  in  the  urine  in  much  larger  quantities,  particu- 
larly after  the  administration  of  chloral,  butyl-chloral,  chloro- 
form, turpentine,  camphor,  morphine,  naphthalene,  curare,  and 
nitrobenzol,  when  it  also  exists  in  combination.  After  the  ad- 
ministration of  chloral  it  appears  as  urochloralic  acid  ;  after  cam- 
phor, as  campho-glycuronic  acid  ;  after  turpentine,  as  turpen- 
glycuronic  acid ;  after  naphthalene,  as  naphthol-glycuronic 
acid,  etc.  It  is  said  to  occur  in  considerable  quantities  in  the 
urine  of  apparently  healthy  people  who  have  not  a  diabetic 
history. 

Glycuronic  acid,  when  pure,  is  not  crystalline,  but  is  ob- 
tained only  as  a  syrup.  It  dissolves  in  alcohol,  is  readily  solu- 
ble in  water,  but  insoluble  in  ether.  Glycuronic  acid  itself  is 
dextrorotatory,  but  when  in  combination,  turns  the  plane  of 
polarized  light  to  the  left.  It  is  converted  into  saccharic  acid 
by  the  action  of  bromine,  and  seems  to  occupy  an  intermediate 
position  between  this  acid  and  gluconic  acid,  CgHj^O,,  obtained 
by  the  oxidation  of  glucose  or  cane  sugar  with  chlorine  or  bro- 
mine. It  reduces  the  salts  of  copper,  bismuth,  silver,  and 
mercury,  and  does  not  undergo  alcoholic  fermentation  with 
yeast.     It  gives  a  crystalline  compound  with  phenylhydrazin. 

1  "Ann.  d.  Cheni.  u.  Pharni.,"  LXXXI,  375. 


170  ABNORMAL  CONSTITUENTS  OF  URINE. 

Isolation. — Glycuronic  acid  is  best  isolated  from  the  urine 
by  the  method  of  Schmiedeberg  and  Meyer,  ^  as  follows  : 

Take  a  large  quantity  of  urine  and  decolorize  by  means  of 
animal  charcoal.  Then  evaporate  it  to  a  syrup,  and  treat  with 
a  large  quantity  of  damp  barium  hydrate,  heating  for  some 
time  over  a  water-bath.  Extract  with  absolute  alcohol,  which 
leaves  glycuronic  acid  and  various  other  substances  undissolved  ; 
mix  the  residue  with  water  and  filter.  Add  more  baryta  to  the 
filtrate,  again  filter,  and  evaporate  the  filtrate  to  a  small  volume 
over  a  water-bath.  An  amorphous  barium  precipitate  separates, 
which  is  washed  with  water,  and  then  decomposed  by  sulphuric 
acid.  The  barium  sulphate  is  then  filtered  off,  the  filtrate  evapo- 
rated down  and  dried  in  a  vacuum,  when  crystals  of  the  anhy- 
dride will  be  obtained. 

Detection. — If  the  urine  reduces  the  salts  of  copper,  and 
does  not  undergo  alcoholic  fermentation  with  yeast,  and  is 
dextrorotatory,  glycuronic  acid  is  probably  present. 


CANE  SUGAR. 
(Saccharose.) 

Cane  sugar,  Cj^H^^Oj^,  is  a  very  uncommon  constituent  of  the 
urine.  It  has  been  found  after  the  ingestion  of  large  quantities 
of  cane-sugar,  but  only  in  rare  instances,  and,  therefore,  is  of  no 
practical  importance  from  a  clinical  standpoint.  It  occasionally 
appears  in  the  urine  from  extraneous  sources,  particularly  when 
the  urine  is  transported  in  a  bottle  that  is  not  clean  or  has  con- 
tained simple  syrup.  It  is  sometimes  added  to  the  urine  by  the 
insane,  or  those  persons  who  are  disposed  to  deceive  the  physi- 
cian or  chemist. 

Cane  sugar,  when  pure,  does  not  reduce  the  salts  of  copper, 
but,  on  account  of  the  fact  that  the  commercial  article  contains 
traces  of  glucose  as  an  impurity,  a  reduction  of  the  cupric  oxide 
may  follow  the  test.  It  crystallizes  in  prismatic  form,  and  its 
aqueous  solutions  rotate  the  polarized  light  strongly  to  the  right, 
-(-  73.8.  When  boiled  with  dilute  hydrochloric  or  sulphuric 
acids,  it  undergoes  the  process  of  ^Hnversion^^ — that  is,  it  takes 
up  a  molecule  of  water  and  is  converted  into  dextrose  and  levu- 
lose,  according  to  the  following  equation  : 

^12^220,1  f  H2O  =  CgH,20g  -f  CpHjjOfi. 

Dextrose.         Levulose. 

On  account  of  the  strong  rotation  of  levulose  the  solution 
now  rotates  to  the  left  instead  of  to  the  right ;  hence  the  term 
inversion. 

1  "  Zeitschr.  f.  physiol.  Ch.,"  in,  422,  1879. 


ACETONE.  171 

Detection. — Traces  of  cane  sugar  may  be  overlooked  in  the 
ordinary  analysis  of  the  urine.  When  present  in  larger  quanti- 
ties, the  specific  gravity  is  usually  very  high,  even  though  the 
normal  solids  are  not  increased  ;  any  glucose  present  is  usually 
found  to  be  in  small  quantities.  The  dextrorotatory  polarization, 
which,  after  inversion,  becomes  levulorotatory,  indicates  the 
presence  of  cane  sugar. 

ACETONE. 

Acetone  is  a  volatile  compound  frequently  found  in  large 
amounts  in  the  urine  under  certain  diseased  conditions. 
According  to  v.  Jaksch,  de  Boeck,  and  A.  Slosse,  normal 
urine  contains  traces  of  acetone  (o.  i  gram  in  twenty -four 
hours — "physiological  acetonuria  ").  Le  Noble  claims, 
however,  that  this  body  is  only  found  in  the  urine  of 
healthy  persons  after  the  use  of  alcohol  and  food  rich  in 
proteid  matter. 

Acetone,  CgHgO,  is  the  typical  member  of  the  group 
known  as  ketones,  and  may  be  prepared  artificially  by  the 
dry  distillation  of  calcium  or  barium  acetate.  It  may  be 
obtained  in  considerable  quantities  by  distillation  of  the 
urine  or  the  blood  of  certain  diabetic  individuals.  The 
peculiar  fruity,  sweet  odor  frequently  noticed  in  the  breath 
and  in  the  urine  of  diabetic  subjects  is  due  to  acetone.  It 
is  a  volatile,  colorless  liquid,  of  a  specific  gravity  of  0.792, 
boiling  at  56.5°  C,  soluble  in  water,  and  characterized  by 
an  ethereal  or  fruity  odor.  The  principal  source  of  acetone 
is  the  decomposition  of  the  proteids  of  the  body  as  well 
as  those  taken  as  food  (v.  Jaksch). 

Clinical  Significance. — The  condition  of  acetonuria  is 
divided  by  v.  Jaksch,  according  to  cause,  into  :  (i)  Febrile  ace- 
tonuria (scarlet  fever,  typhoid  fever,  pneumonia,  measles, 
smallpox,  etc.) ;  (2)  diabetic  acetonuria ;  (3)  acetonuria 
accompanying  certain  forms  of  cancer  independent  of  inani- 
tion ;  (4)  acetonuria  of  starvation  ;  (5)  the  production  of 
acetone  in  psychoses ;  (6)  acetonuria  as  an  expression  of 
autointoxication  ;  (7)  acetonuria  in  derangements  of  diges- 
tion ;  (8)  acetonuria  in  chloroform  narcosis.  The  most 
common  of  these  forms  is  febrile  acetonuria.  It  is  seen  in 
children  as  well  as  in  adults,  and  does  not  belong  to  any 
particular  fever.  In  diabetes  the  appearance  of  acetone  in 
the  urine  indicates  an  advanced  stage  of  the  disease.  The 
ingestion  of  an  abundance  of  nitrogenous  food  tends  to  the 


IT>  AI5NOKMAI,  (( )NSTn"UKNTS  OK  URINK. 

production  of  acctonuria.  riius  it  is  that  tlic  urine  of  dia- 
betics often  contains  a  larger  amount  of  acetone  after  elimi- 
nating starches  and  sugars  from  the  diet,  and  restricting  it 
chiefly  to  nitrogenous  substiuices.  Acctonuria  existing 
alone  (autointoxication  with  acetone)  tends  to  a  favorable 
termination.  Of  greater  importance  are  those  cases  in 
which  much  acetone  is  found  as  an  accompaniment  of  grave 
symptoms  of  cerebral  irritation. 

Detection. — Legal's  Test. —  This  is  a  rough  test,  but  is 
of  sei"vice  on  account  of  being  easy  of  application. 

One-fourth  of  a  test-tube  of  urine  is  treated  with  a  few 
drops  of  a  freshly  {prepared  and  somewhat  concentrated 
solution  of  sodium  nitroprusside,  a  few  drops  of  acetic 
acid  are  added  to  prevent  the  reaction  with  kreatinin,  and 
the  mixture  is  then  rendered  alkaline  with  ammonic  or  sodic 
hydrate.  The  mixture  gradually  develops  a  red  color, 
which  increases  to  a  deep  purple-red  color.  In  the  ab.sence 
of  acetone  the  red  or  purple-red  tint  does  not  form. 

For  purposes  of  greater  accuracy  it  is  necessary  to  distil 
the  urine  (500  to  lOOO  c.c),  after  the  addition  of  a  little 
phosphoric  acid  (i  gram  per  liter),  to  prev^ent  the  evolution 
of  gases  ;  the  first  10  to  30  c.c.  of  the  distillate  are  used 
for  the  following  tests  : 

Lieben's  Test. — A  few  cubic  centimeters  of  the  distillate 
are  treated  with  several  drops  of  a  dilute  solution  of  iodo- 
potassic  iodide  and  sodic  hydrate.  In  the  presence  even 
of  traces  of  acetone,  a  precipitation  of  iodoform  in  crys- 
talline form  occurs,  which  may  be  readily  recognized  by 
its  odor. 

Quantitative  Estimation  of  Acetone. — The  method  of 
Messinger,  as  modified  by  Huppert,  is  best  adapted  to  the  esti- 
mation of  acetone  in  urine,  and  is  based  upon  the  observation 
of  Lieben,  that  acetone  gives  rise  to  the  formation  of  iodoform 
when  treated  with  iodine  in  an  alkaline  solution.  If,  then,  a 
solution  of  acetone  be  treated  with  a  known  amount  of  iodine, 
the  quantity  present  is  determined  by  retitrating  the  iodine  that 
was  not  used  in  the  formation  of  iodoform. 

Solutions  Required. — (i)  Acetic  acid  (50  per  cent,  solution)  ; 
(2)  sulphuric  acid  (12  per  cent,  solution);  (3)  sodic  hydrate 
solution  (50  per  cent.)  ;  (4)  a  decinormal  solution  of  iodine  ; 
(5)  a  decinormal  solution  of  sodium  thiosulphate. 

Process. — One  hundred  cubic  centimeters  of  urine,  or  less  if 
much  acetone  be  present   as  determined  by  Legal's    test,  are 


ACETONE.  173 


treated  with  2  c.c.  of  the  acetic  acid  solution,  and  distilled  until 
seven-eighths  of  the  total  amount  has  passed  over.     The  dis- 
tillate is  received  in  a  retort  that  is  connected  with  a  bulb  appa- 
ratus filled  with  water.     As  soon  as  seven-eighths  of  the  urine 
has   distilled    over,   a   small    amount    of   the    distillate    of  the 
remainder  is  tested  for  acetone  by  Lieben's  method.     Should  a 
positive  reaction  be  obtained,   it   will   be   necessary  either   to 
repeat  the  entire  process  with  less  urine,  diluted  to  about   200 
c.c,  or  to  add  about   100  c.c.  of  water  to  the  residue  and  to 
distil  until  all  the  acetone  has  been  driven  over.     The  distillate 
is  then  treated  with  i  c.c.  of  the  sulphuric  acid,  and  redistilled. 
The  addition  of  the  acetic  acid  and  of  the  sulphuric  acid,  respect- 
ively, serves  the  purpose  of  holding  back  the  phenol  and  the 
ammonia.       Should    the    first   distillate   contain    nitrous   acid, 
which  may  be  recognized  by  the  addition  of  a  little  starch-paste 
containing  a  trace  of  potassium  iodide,  when  the  solution  will 
turn  blue,  this  is  removed  by  adding  a  little  urea.     The  second 
distillate  is  received  in  a  bottle  provided  with  a  well-ground 
glass  stopper,  and  holding  about  one  liter.      To  prevent    the 
escape  of  acetone,  the  glass  stopper  is  replaced  by  a  doubly  per- 
forated cork,  through   which  two  glass  tubes  pass,  one  to  the 
distilling  apparatus,  the  other  to  the  bulb  apparatus.     The  dis- 
tillate is  then  treated  with  a  carefully  measured  quantity  of  the 
decinormal  solution  of  iodine — about  10  c.c.  for  each  100  c.c. 
of  urine  used — and  sodic  hydrate  solution,   which  should  be 
added  drop  by  drop  until  the  blue  color  has  disappeared  and 
the  iodoform  separates  out.     To  this  end  a  slight  excess  of  the 
solution  must  be  added.     Should  ammonia  be  present,  a  blackish 
cloud  will  be  observed  at  the  zone  of  contact  of  the  .sodic  hydrate 
and  the  iodine  solution,  and  it  will  be  necessary  to  repeat  the 
entire  process.     The  bottle  is  closed  and  shaken  for  about  one 
minute.     The  solution    is   then   acidulated  with    concentrated 
hydrochloric  acid,  when  the  mixture  assumes  a  brown  color  if 
io-dine  be  present  in  excess.     If  this  does  not  occur,  more  of  the 
iodine  solution  must  be  added,  and  the  process  repeated  until 
an  excess  is  present.     The  excess  is  then  retitrated  with  the 
thiosulphate  solution  until  the  solution  presents  a  faint  yellow 
color.      A   few  cubic  centimeters  of  starch  solution  are  then 
added,  and  the  titration  continued  until  the  last  trace  of  blue 
has  disappeared.     The  number  of  cubic  centimeters  employed 
in  the  titration  is  finally  deducted  from  the  total  amount  of  the 
iodine   solution  added,   and    the    result   multiplied   by  0.967. 
The  figure  thus  obtained  will  then  indicate,  in  terms  of  milli- 
grams, the  amount  of  acetone  contained  in  the  100  c.c.  of  urine, 
as  I  c.c.  of  the  thiosulphate  solution  is  equivalent  to  i  c.c.  of 
the  iodine  solution,  or  to  0.967  milligrams  of  acetone. 


174  ABNORMAL  CONSTITUENTS  OF  URINE. 


DIACETIC  ACID. 

Diacetic  acid,  also  termed  aceto-acetic  or  ethyl-diacctic 
acid,  CgHjp03,  sometimes  appears  in  the  urine.  Its  pres- 
ence must  always  be  regarded  as  abnormal.  Urine  con- 
taining diacetic  acid  is  always  rich  in  acetone,  for  which 
diacetic  acid  is  often  mistaken.  These  two  bodies  e.xist  in 
the  urine  independently,  although  by  the  action  of  alkalies 
diacetic  acid  is  readily  converted  to  acetone,  alcohol,  and 
COg,  as  shown  by  the  following : 

C6H10O3  -f  H,0  =  CjH.O  +  C,Hp  +  CO, . 

Diacetic  acid.  Acetone.       Alcohol. 

Whether  a  similar  decomposition  takes  place  in  the  blood 
remains  still  an  open  question. 

Diacetic  acid  is  a  colorless  liquid,  which  gives  a  charac- 
teristic Bordeaux-red  color  with  a  solution  of  ferric  chloride. 
But  this  color  with  ferric  chloride  may  be  produced  by  the 
presence  of  other  substances  in  the  urine,  such  as  salicylic 
acid,  carbolic  acid,  antipyrin,  thallin  (Legal  and  Hammar- 
sten)  ;  also  acetic  and  formic  acids,  sulpho-  (thio-)  cyanates, 
and  /5-hydroxybutyric  acid.  Diacetic  acid  is  distinguished 
from  these  substances  by  the  fact  that,  if  the  urine  be  pre- 
viously boiled,  diacetic  acid  does  not  give  the  ferric  chloride 
reaction,  while  the  other  substances  continue  to  give  the 
Bordeaux-red  color  as  before.  Furthermore,  that  salicylic 
acid,  carbolic  acid,  etc.,  are  not  extracted  from  the  urine  by 
ether,  whereas  diacetic  acid  is  soluble  in  ether. 

Clinical  Significance. — As  already  mentioned,  the  pres- 
ence of  diacetic  acid  in  the  urine  (diaceturia)  is  always 
pathologic,  and  should  in  general  be  considered  a  serious 
symptom.  Diacetic  acid  is  frequently  found  in  the  urine  in 
diabetes  mellitus,  in  fevers,  and  also  idiopathically  as  a  form 
of  autointoxication  (diacetemia).  It  is  of  common  occur- 
rence in  the  urine  of  children  as  a  concomitant  of  fever 
(v.  Jaksch),  and  is  then  generally  devoid  of  serious  impor- 
tance ;  but  in  children  or  adults  suffering  from  diabetes  it  is 
a  symptom  of  grave  import.  Diaceturia  is  most  common 
in  the  advanced  stages  of  diabetes  mellitus,  and  particularly 
in  children  and  persons  under  the  age  of  thirty.  The  oc- 
currence of  this  symptom  may  be  looked  upon  as  a  very 
probable  forerunner  of  diabetic  coma  and  rapid  death.  The 
author's  experience  has  led  him  to  make  an  unfavorable  prog- 


BILE.  175 

nosis  in  all  cases  of  diabetes  mellitus  (under  thirty  years  of 
age)  in  which  the  urine  contains  diacetic  acid. 

The  form  of  autointoxication  of  which  diaceturia  is  the 
chief  index  is  usually  rapidly  fatal,  being  accompanied  by 
such  symptoms  as  vomiting,  dyspnea,  jactitation,  and  coma, 
without  evidence  of  any  other  pathologic  process. 

Detection. — The  process  suggested  by  v.  Jaksch  is  most 
reliable,  and  is  as  follows  :  To  the  urine  a  fairly  concen- 
trated solution  of  perchloride  of  iron  is  cautiously  added, 
and  if  a  phosphatic  precipitate  forms,  this  is  removed  by 
filtration,  and  more  of  the  perchloride  of  iron  solution  sup- 
plied. If  the  Bordeaux-red  color  appears,  one  portion  of 
the  urine  is  boiled,  while  another  portion  is  treated  with 
sulphuric  acid  and  extracted  with  ether.  If  now  the  urine 
that  has  been  boiled  gives  no  reaction  with  the  perchloride 
of  iron  solution,  while  the  ethereal  extract  shows  a  claret- 
red  color  with  the  iron  solution,  diacetic  acid  is  probably 
present,  particularly  if,  at  the  same  time  (on  testing  the 
urine  directly  and  its  distillate),  it  is  found  to  be  rich  in 
acetone. 

The  urine  to  be  tested  should  be  perfectly  fresh,  for  the 
reason  that  in  a  urine  that  has  begun  to  decompose  the 
diacetic  acid  takes  up  a  molecule  of  water  and  splits  into 
acetone,  alcohol,  and  carbon  dioxide. 


BILE. 

Of  the  constituents  of  bile,  the  biliary  pigments  and 
acids  chiefly  concern  us  here.  Another  constituent  of  bile 
— viz.,  cholesterin — has  never  yet  been  found  in  the  urine 
in"  jaundice,  but  has  been  met  with  in  considerable  quantities 
in  other  connections. 

BILIARY  PIGMENTS. 

A  urine  containing  bile  is  always  abnormally  colored. 
The  chief  unaltered  biliary  pigment  is  bilirubin,  which  is  an 
intermediate  product  in  the  body  between  hemoglobin  and 
urobilin.  (See  p.  91.)  When  bilirubin  (orange-yellow) 
becomes  oxidized,  either  by  exposure  to  the  air  or  by  re- 
agents, the  first  and  most  important  oxidation  product  is 
biliverdin  (green)  ;  then  follow  the  less  important  products, 
bilicyanin  (blue),  bi/ifnscin,  hiliprasiii ,  and  finally  cJiolctelin  (.^). 
Bilirubin  is  in  the  urine  in  a  free  state  ;  but  in  biliary  calculi, 


176  ABNORMAL  CONSTITUENTS  OF  URINE. 

in  which  it  is  often  present  in  abundance,  it  exists  as  a  cal- 
cium compound — bilirubin  caiman. 

The  color  of  a  bile-containing  urine  is  either  greenish-yel- 
low, yellowish-brown,  deep  brown,  greenish-brown,  or,  on 
standing  exposed  to  the  air,  may  be  nearly  pure  green.  On 
shaking  the  urine  it  gives  a  persistent  greenish-yellow  or  yel- 
low froth  or  foam.  Furthermore,  if  a  piece  of  filter-paper  or 
linen  be  moistened  with  such  urine,  it  retains  a  permanent 
yellow  color  on  drying.  A  jaundiced  urine  almost  invari- 
ably contains  an  excess  of  urobilin  and  indoxyl.  A  urine 
from  which  the  bile  has  recently  disappeared  is  usually 
highly  colored,  due  to  the  large  excess  of  urobilin. 

A  bile-containing  urine  is  always  albuminous.  The 
chief  proteid  appears  to  be  nucleo-albumin,  which  is 
usually  accompanied  by  traces  of  serum  albumin.  In  this 
connection  it  is  noteworthy  that  the  nitric  acid  test  for 
albumin  can  not  be  satisfactorily  used  for  the  detection  of 
slight  traces,  on  account  of  the  amount  of  coloring-matter 
set  free  by  the  acid,  thus  obscuring  a  faint  zone  of  albumin. 
For  this  reason,  therefore,  in  a  urine  containing  much  bile, 
the  heat  test  for  albumin  is  preferable.  The  sediment 
usually  contains  a  large  number  of  renal  epithelial  cells, 
which  are  more  or  less  colored  by  the  bile  pigment.  Not 
infrequently,  they  have  attached  to  their  surfaces  stellate 
clusters  of  bilirubin  crystals,  which  have  a  yellowish-brown 
color  ;  also  small,  irregular,  brown,  bilirubin  granules.  (See 
p.  224.)  The  sediment  also  contains  renal  casts  and  abnor- 
mal blood  globules,  free  and  adherent  to  casts,  the  result  of 
the  irritation  of  the  kidneys  by  the  bile.  If  more  than  a 
mere  trace  of  bile  pigment  be  present  in  the  urine,  the  organ- 
ized elements  of  the  sediment  are  invariably  stained  yellow 
or  yellowish-brown. 

Clinical  Significance. — Bile  pigments  occur  in  the  urine 
in  every  case  of  jaundice — in  other  words,  in  every  case  in 
which  there  is  an  obstruction  to  the  outflow  of  bile  from 
the  bile-ducts  {Jtepatogenous  icterus).  Thus  they  are  found 
in  a  variety  of  pathologic  conditions  of  the  liver,  of  which 
the  most  common  are  catarrhal  jaundice,  obstruction  in  the 
common  bile-duct  by  biliary  calculi,  cancer,  and  cirrhosis 
of  the  liver.  They  may  also  appear  in  the  urine  incases 
of  destruction  of  the  red  blood  globules,  as  in  severe  infec- 
tious conditions,  phosphorus-poisoning,  etc.  {Jiematogcnous 
icterus  ).     Bile  pigments  often  make  their  appearance  in  the 


BILE.  177 

urine  before  there  is  much  coloration  of  the  conjunctivje,  or 
any  yellow  color  in  the  skin. 

Detection. — Marechalt's  Test. — Take  about  one  finger- 
breadth  of  an  alcoholic  solution  of  iodine  (not  too  strong) 
in  a  test-tube,  and  underlie  with  urine  by  allowing  it  to  flow 
down  the  side  of  the  inchned  test-tube  from  a  pipette  placed 
above  the  level  of  the  iodine.  If  biliary  pigments  are 
present,  a  green  color  appears  just  below  the  point  of  con- 
tact of  the  two  fluids,  and  remains  for  some  time,  even  for 
twenty-four  hours.  In  this  test  the  possibility  of  confound- 
ing with  indoxyl  is  said  to  be  excluded. 

Gtnelin's  Test. — This  test  is  performed  in  two  ways  : 

1.  A  quantity  of  urine  is  placed  in  a  wine-glass,  and  a 
small  quantity  of  concentrated  nitric  acid  is  allowed  to  flow 
carefully  down  the  side  of  the  wine-glass  to  underlie  the  urine, 
as  described  in  the  nitric  acid  test  for  albumin.  If  bihaiy 
coloring-matters  are  present,  at  the  point  of  union  between 
the  urine  and  the  acid  a  play  of  colors  will  very  soon 
appear,  which,  if  typical,  should  be  green,  blue,  violet,  red, 
and  yellow  or  yellowish-green,  in  the  order  named.  Often, 
however,  one  or  more  colors  are  wanting.  The  green  is 
most  constant,  the  first  green  being  indispensable  to  prove 
the  presence  of  bile  ;  but  violet,  shading  into  red  and  yellow, 
is  also  very  constantly  seen.  The  other  colors  may  be  pro- 
duced by  other  coloring-matters,  especially  indoxyl. 

2.  The  test  can  also  be  applied  by  placing  a  drop  of  the 
suspected  urine  on  a  porcelain  plate,  and  allowing  a  drop 
of  the  fuming  nitric  acid,  which  has  been  placed  adjacent,  to 
gradually  mingle  with  the  urine.  The  same  play  of  color 
occurs. 

Another  method  consists  in  precipitating  the  urine  with 
a  small  amount  of  milk  of  lime.  A  small  portion  of  this 
precipitate  is  then  treated  with  a  drop  of  concentrated  nitric 
acid,  and  if  bile  pigments  are  present,  a  play  of  colors,  like 
that  seen  in  Gmelin's  test,  occurs. 

The  two  tests  for  biliary  pigments  just  described  are  quite 
satisfactory,  providing  the  urine  contains  a  large  amount  of 
bile,  but  they  are  far  from  conclusive  when  the  urine  con- 
tains minute  traces  of  biliary  pigments.  Various  other  tests 
for  bile  pigments  have  been  advised,  but  all  possess  greater 
shortcomings  than  Marechalt's  or  Gmelin's  tests,  and  many 
of  them  are  valueless.  In  the  hands  of  the  writer  Mare- 
chalt's test  is  the  most  serviceable  of  all  tests,  especially 


178  ABNORMAL  CONSTITUENTS  OF  URINE. 

when  applied  in  the  manner  previously  outlined.  It  is  to  be 
said,  however,  that  a  normal  urine  often  reacts  with  iodine 
so  as  to  suggest  a  trace  of  bile  when  it  is  evident  that  no 
bile  pigments  are  present.  It  is  certain  that  this  subject 
needs  further  investigation  in  order  to  be  able  to  demon- 
strate satisfactorily  the  presence  of  traces  of  bile  pigments 
in  urine. 

BILIARY  AQDS. 

Any  interference  with  the  discharge  of  bile  from  the  liver 
or  common  bile-duct  results  in  the  passage  of  the  bile  con- 
stituents into  the  blood  and  their  elimination  by  the  urine 
{liepatogcnous  icterus).  But  bile  pigments  may  also  pass  into 
the  urine  under  other  circumstances,  especially  when  there 
is  destruction  of  the  red  blood-corpuscles  through  poisoning 
by  ether,  chloroform,  arseniureted  hydrogen,  phosphorus, 
and  in  grave  infectious  diseases.  In  this  second  form  of 
icterus  the  blood  coloring-matter  appears  to  be  transformed 
into  bile  pigment  elsewhere  than  in  the  liver,  possibly  in  the 
blood,  and  thus  it  is  that  we  have  the  so-called  licniatogcnous 
icterus.  Only  the  bile  pigments  appear  in  the  urine  in  these 
cases,  while  in  hepatogenous  icterus  the  urine  contains  the 
bile  pigments  and  bile  acids  at  the  same  time  (Leyden). 
This  arbitrary  distinction,  however,  can  not  be  fully  main- 
tained in  all  cases.  It  is  certainly  true  that  the  presence 
of  more  than  mere  traces  of  bile  acids  in  the  urine  indicates 
the  existence  of  hepatogenous  jaundice,  but  cases  of  absorp- 
tion icterus  undoubtedly  occur  in  which  no  bile  acids  can  be 
detected  in  the  urine. 

According  to  Dragendorf,  Vogel,  and  Oliver,  traces  of 
bile  acids  occur  in  normal  urine,  but  Hoppe-Seyler  and 
Udranszky  both  hold  the  opposite  view.  This  question 
must  be  considered  unsettled  until  confirmatory  evidence 
bearing  upon  one  or  the  other  view  is  at  hand. 

All  bile  acids  can  be  conveniently  divided  into  two  groups 
— the  glycocholic  and  the  taurocJiolic  acid  groups.  The  glyco- 
cholic  acids  contain  nitrogen,  but  are  free  from  sulphur, 
and  can  be  split,  with  the  addition  of  water,  into  glycocoU 
and  an  acid  free  from  nitrogen — cholic  acid.  The  tauro- 
cholic  acids  contain  nitrogen  and  sulphur,  and  are  split, 
with  the  addition  of  water,  into  taurin,  which  contains  sul- 
phur and  cholalic  acid.  The  existence  of  different  glyco- 
cholic and  taurocholic  acids  depends  on  the  fact  that  there 


BILE.  179 

are  several  cholalic  acids.  These  two  groups  of  acids  exist 
in  the  urine  chiefly  as  salts  of  sodium. 

Clinical  Significance. — As  already  intimated,  bile  acids 
are  most  commonly  found  in  the  urine  in  cases  of  obstruc- 
tive jaundice — that  is,  in  the  Jiepatogcnous  form,  and  not  gen- 
erally present  in  the  Iieviatogeiious  form  of  icterus.  This  very 
general  rule,  however,  is  subject  to  much  variation,  and, 
therefore,  the  determination  of  the  presence  of  bile  acids 
can  not  be  considered  especially  diagnostic  of  the  existence 
of  hepatogenous  jaundice.  They  are  present  in  the  urine 
of  hepatic  congestion,  cirrhosis,  and  hepatic  tumors  ;  also 
in  carcinoma  and  severe  acute  bilious  attacks.  They  have 
also  been  found  in  anemia,  hemoglobinuria,  scurvy,  and 
splenic  leukemia.  They  are  much  less  common  in  the 
urine  in  amyloid  infiltration  of  the  liver. 

Tests  for  bile  acids  are  not  usually  made  in  the  routine 
analysis  of  urine.  In  fact,  for  purposes  of  diagnosis,  the 
detection  of  bile  pigments  is  generally  sufficient.  It  is  impos- 
sible to  apply  satisfactorily  the  ordinary  test — Pettenkofer's 
— for  bile  acids  directly  to  the  urine  ;  they  must,  therefore, 
be  isolated. 

Isolation. — The  simplest  method  of  obtaining  the  biliary 
acids  is  the  one  suggested  by  Dr.  Tyson,  ^  and  is  as  fol- 
lows :  "  Six  or  eight  ounces  (i8o  to  240  c.c.)  of  the  sus- 
pected urine  are  evaporated  to  dryness  over  a  water-bath. 
The  residue  thus  obtained  is  treated  with  an  excess  of  abso- 
lute alcohol,  filtered,  and  the  filtrate  treated  with  an  excess 
of  ether  (12  to  24  times  its  bulk),  by  which  the  bile  acids,  if 
present,  are  precipitated.  These  are  then  removed  by  fil- 
tration, and  redissolved  in  distilled  water.  The  solution  is 
then  decolorized  by  passing  through  animal  charcoal,  and 
the  resulting  colorless  fluid  subjected  to  Pettenkofer's  test." 

According  to  Hoppe-Seyler,  the  bile  acids  can  be  sepa- 
rated from  the  urine  in  the  following  manner :  Render 
the  urine  alkaline  with  ammonic  hydrate,  and  precipitate 
directly  with  basic  acetate  of  lead  ;  wash  the  precipitate 
with  water,  dry  by  gentle  heat,  heat  several  times  with 
absolute  alcohol,  and  filter  while  hot.  To  the  alcoholic 
solution  of  lead  salts  of  the  bile  acids  add  a  few  drops  of 
sodic  hydrate  and  evaporate  to  dryness.  Extract  the 
residue  with  absolute  alcohol  by  the  aid  of  heat ;    evapo- 

1"  Philadelphia  Medical  Times,"  July  5,  1873. 


180  ABNORMAL  CONSTITUENTS  OF  URINE. 

rate  the  solution  to  a  small  volume,  and  shake  vvitii  an 
excess  of  ether,  whereby  the  biliary  salts  are  separated 
as  an  amorphous  precipitate.  Filter,  dissolve  the  precipi- 
tate in  distilled  water,  and  apply  Pettenkofer's  test. 

Dragendorff  has  shown  that  the  bile  acids  can  be  extracted 
from  urine  that  has  been  acidulated  with  hydrochloric  acid 
by  shaking  with  chloroform. 

If  ox  bile  be  added  to  urine,  Pettenkofer's  reaction  can 
generally  be  demonstrated  without  separating  the  bile  salts 
as  just  indicated,  providing,  however,  the  color  of  the  urine 
used  is  normal  or  pale,  and  not  high. 

Detection. — Pettenkofer's  Test  for  Bile  Acids. — The 
test,  as  usually  applied,  is  as  follows  : 

Process. — Bile,  which  may  be  considerably  diluted,  or  a 
dilute  solution  of  bile  salts  or  acids,  is  mixed  in  a  porce- 
lain dish  with  a  iQ\N  drops  of  a  lo  per  cent,  solution  of 
cane  sugar.  Concentrated  sulphuric  acid  is  then  added  to 
the  mixture,  with  constant  stirring,  to  an  extent  not  ex- 
ceeding two-thirds  of  its  volume,  the  addition  of  the  acid 
being  so  regulated  that  the  temperature  of  the  mixture  is 
not  allowed  to  rise  abov^e  70°  C.  A  brilliant  cherry-red 
changing  to  a  reddish-purple  color  soon  makes  its  ap- 
pearance. On  standing  for  some  time  the  color  becomes 
darker  and  assumes  more  of  a  blue  tint.  The  reaction 
may  also  be  obtained  by  the  addition  of  first  the  acid  and 
then  the  sugar  solution.  The  success  of  the  test  depends 
upon  keeping  the  temperature  of  the  mixture  below  70'^  C. 
(a  cold  water-bath  may  be  used),  and  the  avoidance  of  any 
excess  of  sugar,  which,  by  being  charred  by  the  acid,  gives 
a  brown  color  and  masks  the  typical  purple.  To  avoid 
this,  Drechsel  recommends  the  use  of  phosphoric  acid 
(5  of  the  glacial  acid  to  i  of  water)  instead  of  sulphuric  acid. 
In  this  case  the  solution  must  be  heated  by  immersion  in 
boiling  water. 

According  to  Schenk,^  if  the  typical  purple  solution  is 
diluted  with  alcohol,  it  shows  with  the  spectroscope  a  char- 
acteristic absorption  spectrum,  consisting  of  two  absorption 
bands,  one  between  D  and  E,  bordering  on  E,  and  a  second 
between  E  and  F,  adjoining  F. 

Pettenkofer's  reaction  depends  upon  the  presence  of 
cholalic  (or  cholic)  acid,  a  constituent  of  the  bile  acids  ;  also 

^  "  Jahresber.  f.  ThierCh.,"  II,  232. 


BILE.  181 

upon  the  formation  of /w/z/'/yV  (also  known  as  furfuralde- 
hyde)  which  results  from  the  action  of  the  sulphuric  acid 
upon  the  sugar,  the  characteristic  color  arising  from  the  in- 
teraction of  the  furfurol  with  the  cholalic  acid. 

This  test  is  far  from  satisfactory  when  applied  directly  to 
the  urine,  even  when  the  bile  acids  are  present  in  consid- 
erable amount,  since,  on  the  one  hand,  urinary  pigments 
and  other  substances  are  charred  by  the  sulphuric  acid, 
thus  interfering  with  the  brilliancy  of  the  reaction  ;  and, 
secondly,  if  the  urine  contains  proteids,  cholesterin,  amyl 
alcohol,  and  various  other  substances,  a  purple  color  is  pro- 
duced which  closely  resembles  that  due  to  bile  acids. 

Oliver's  Peptone  Test. —  This  test  is  based  on  the  physi- 
ologic fact  that,  when  the  products  of  gastric  digestion,  pep- 
tone and  parapeptone,  which  pass  from  the  stomach  in  an  acid 
medium,  meet  with  the  bile  in  the  duodenum,  they  are  precipi- 
tated. So,  too,  albuminous  urine,  or  urine  charged  with  pep- 
tone, is  precipitated  by  a  solution  of  bile  salts, — sodium  glyco- 
cholate  or  taurocholate.  Thus  an  acid  solution  of  peptone  is 
recommended  and  is  prepared  as  follows : 

Pulverized  peptone  (Savary  and  Moore),  30  grains;  salicylic 
acid,  4  grains;  acetic  acid,  30  minims;  and  distilled  water  up 
to  8  fluidounces.      Filter  until  a  clear  filtrate  is  obtained. 

Process. — To  60  minims  of  this  test  solution  add  20  minims 
of  perfectly  clear  urine  which  has  been  previously  rendered  nor- 
mally acid  if  alkaline,  and  which  has  been  reduced  to  a  specific 
gravity  of  1008.  If  the  proportion  of  bile  salts  be  normal  or 
subnormal,  no  immediate  reaction  occurs,  but  in  a  short  time  a 
mere  tinge  of  milkiness  appears.  If  in  excess,  a  distinct  tur- 
bidity promptly  appears,  becoming  more  intense  in  a  minute  or 
twQ,  the  degree  of  opacity  being  directly  proportionate  to  the 
amount  of  bile  acids  present.  On  agitation  the  opalescence 
diminishes,  and  may  finally  disappear,  but  is  restored  on  adding 
more  of  the  test  solution. 

Approximate  Quantitative  Test. —  This  is  based  upon  a 
permanent  standard  of  oi)acity  provided  by  mixing  equal  pro- 
portions of  the  test  solution  and  normal  urine  reduced  to  the 
specific  gravity  of  1008.  To  60  minims  of  the  test  solution 
add  the  suspected  urine  diluted  to  a  specific  gravity  of  1008, 
usually  10  to  20  minims  at  a  time,  allowing  a  minute  to  elapse 
after  each  addition,  until  the  opacity  induced  is  exactly  equal 
to  or  slightly  exceeds  that  of  the  standard,  the  tubes  being  held 
to  the  light,  shaded  by  a  dark  background.  If  50  or  60  minims 
bring  up  the  opacity  to  that  of  the  standard,  the  proportion  of 
bile  salts  does  not  exceed  the  normal.      Any  smaller  quantity 


182  ABNORMAL  CONSTITUENTS  OF  URINE. 

required    indicates  an  excess,   while    the   smaller  the    amount 
needed,  the  larger  the  proportion  of  bile  salts  present. 

OLIVER'S  STANDARD  TABLE. 


Minims. 

Urine. 

Drops. 

Percentage  of  Increase  over 
the  Normal  Standard. 

I 

or 

2 

=: 

6000 

2 

or 

4 

= 

3OCX) 

3 

or 

6 

= 

2000 

4 

or 

8 

= 

1500 

5 

or 

10 

= 

1200 

lO 

or 

20 

=r 

600 

15 

or 

30 

= 

400 

20 

or 

40 

= 

300 

25 

or 

50 

= 

240 

30 

or 

60 

= 

100 

35 
40 

or 
or 

70 
80 

= 

83 

66 

45 

or 

90 

= 

50 

This  test,  according  to  Dr.  Oliver,  is  so  delicate  that  one 
part  of  bile  salts  can  readily  be  detected  in  18,000  to  20,000 
parts  of  a  solution  of  sodium  chloride.  An  increase  over  700 
per  cent,  beyond  the  normal  is  rarely  encountered.  Oliver  has 
yet  to  find  anything  that  interferes  with  this  test  for  bile  acids 
in  the  urine. 

Dr.  Oliver  has  also  devised  a  peptone  test-paper  that  he  con- 
siders permanent,  reliable,  and  convenient  for  use. 


EHRLICH'S  DIAZO  REACTION. 

This  reaction  was  first  described  by  Ehrlich  ^  in  1882. 
It  depends  upon  the  peculiar  color  produced  in  the  urine 
(and  more  particularly  in  the  foam)  by  the  action  of  diazo- 
benzol-sulphonic  acid  upon  certain  unknown  substances  in 
the  presence  of  an  excess  of  ammonic  hydrate. 

The  following-  solutions  are  neces.saiy  for  the  reaction  : 

Solution  A. 

Sulphanilic  acid  (.saturated  aqueoi:s  solution)  .     200  c.c. 
Hydrochloric  acid  (concentrated) 10   " 

Solution  B. 

Sodium  nitrite       i    " 

Distilled  water 200  " 

These  solutions  {A  and  E)  are  to  be  kept  separate,  in 
well-.stoppered  bottles,  and  preferably  in  a  dark  place.  It 
is  necessary  to  have  the  sodium  nitrite  solution  as  fresh  as 
possible,  and,  since  it  decomposes  in  the  course  of  a  few 

'  "Zeitschr.  f.  klin.  Med.,"  IV,  285-288. 


EHRLICH'S  DIAZO  REACTION.  183 

weeks,  it  is  advisable   to   keep   only  a  small  quantity  of  it 

on  hand.  .  ,   , 

Method  of  Applying  Test.-Take  in  a  test-tube  a  mix- 
ture of  40  parts  of  solution  A  and  i  part  of  solution  i>  ; 
add  an  equal  volume  of  urine;  shake  the  whok  mixture 
thoroughly,  and  allow  an  excess  of  amnionic  hydrate  to 
run  slowly  down  the  side  of  the  tube.  If  the  diazo  reac- 
tion be  present,  the  foam  will  be  colored  pink,  and  tha 
portion  which  is  acted  upon  by  the  amnionic  hydrate  will 
have  a  crimson  color.  When  the  test-tube  is  inverted,  the 
entire  column  of  liquid  in  the  tube  will  be  found  to  have  a 
crimson  color,  while  the  foam  still  remains  pink. 

Ehrlich  found  that  this  reaction  was  almost  constantly 
present  in  the  urine  of  typhoid  fever.  He  also  obtained 
the  reaction  in  the  urine  of  a  variety  of  other  diseases, 
mostly  acute  febrile  diseases,  but  in  these  its  occurrence 
was  not  constant.  He.  therefore,  called  attention  to  the 
value  of  the  diazo  reaction  as   an   aid  in  the  diagnosis  of 

typhoid  fever.  •       •     ^u 

Since  the  discovery  of  this  peculiar  reaction  m  the  urine 
considerable  discussion  has  arisen  as  to  its  clinical  value  in 
connection  with  the  diagnosis  of  typhoid.  It  is  sate  to 
sav  that  the  reaction,  as  ordinarily  applied,  has  met 
with  much  disfavor,  owing  partly  to  the  fact  that  it  is 
frequently  obtained  in  the  urines  of  a  number  of  other  dis- 
eases such  as  pulmonary  phthisis,  pneumonia,  pleurisy, 
scarlet  fever,  diphtheria,  measles,  erysipelas,  acute  miliary 
tuberculosis,  syphilis,  carcinoma,  puerperal  septicemia  and 
other  septic  conditions,  acute  and  chronic  rheumatism,  etc., 
and  partly  on  account  of  the  failure  of  some  observers  to 
follow  the  methods  laid  down  by  Ehrlich. 

Dr  Charles  L.  Greene,  of  St.  Paul,  Minn.,  who  has 
made  a  very  careful  study  ^  of  this  subject,  has  found 
that  much  more  satisfactory  results  are  obtained  by 
modifying  the  proportions  of  solutions  A  and  i>.  Me, 
therefore  recommends  the  use  of  a  test  solution,  which 
shall  consist  of  100  parts  of  solution  A  and  i  part  ot 
solution  B,  instead  of  40  parts  of  A  and  i  part  of  B  as 
ordinarily  used.  In  a  study  of  3 1 5  cases  representing 
many  of  the  common  forms  of  disease  he  obtained  by 
means  of  this  modified  test  solution  characteristic  reactions 


1  "  Medical  Record,"  Nov.  14,  i J 


184  ABNORMAL  CONSTITUENTS  OF  URINE. 

in  only  five  diseases  :  i.  c,  typhoid  fever,  95  per  cent.  ; 
pneumonia,  9  per  cent.  ;  carcinoma,  50  per  cent.  ;  pulmon- 
ary phthisis,  12.5  per  cent.;  and  septicemia,  75  percent. 
He  firmly  believes  that  all  cases  of  severe  typhoid  will 
show  a  diazo  reaction  if  the  test  is  properly  applied  during 
the  height  of  the  disease — that  is,  between  the  tenth  and 
eighteenth  days. 

Von  Jaksch,!  on  the  other  hand,  believes  that  the  so- 
called  diazo  reaction  is  always  due  to  the  presence  of  ace- 
tone, and  he  considers  the  reaction  rather  an  uncertain  test 
for  acetone  than  a  test  for  anything  else. 

The  author  can  recommend  Greene's  modified  test  solu- 
tion, since  by  its  use  positive  reactions  are  obtained  in  a 
much  smaller  number  of  diseases  than  by  the  use  of  the 
original  Ehrlich  solution.  However,  he  can  not  agree  with 
Greene  as  to  its  diagnostic  value  in  typhoid,  owing  to  the 
fact  that  in  some  cases  of  this  disease,  especially  the  milder 
forms,  no  characteristic  reactions  can  be  obtained  at  any 
time  during  the  disease.  It  is  certain  that  many  of  the 
urines  that  show  this  reaction  contain  acetone,  but  further 
investigation  is  necessary  to  prove  that  the  so-called  diazo 
reaction  is  directly  or  indirectly  due  to  acetone. 


VARIOUS  METALLIC  SUBSTANCES. 

Various  metallic  substances,  notably  lead,  arsenic,  and 
mercury,  are  eliminated  in  the  urine,  and,  when  suspected, 
should  be  carefully  sought  for. 

Arsenic  may  be  absorbed  in  either  small  or  large  amounts, 
and  is  quite  readily  eliminated  in  the  urine  without  the  aid 
of  drugs.  It  is,  to  a  slight  degree,  cumulative — that  is, 
sufficient  arsenic  may  be  absorbed  in  three  or  four  days' 
time  to  require  from  sixty  to  ninety  days  for  its  complete 
elimination. 

Lead  is  usually  absorbed  in  very  small  quantities,  and 
the  cause  of  its  ver)--  slow  elimination  from  the  body  is 
probably  its  accumulation  in  the  system  as  a  fixed  con- 
stituent of  the  tissues.  The  natural  channel  of  elimination 
is  by  way  of  the  kidneys,  and  in  order  that  it  should  become 
a  constituent  of  the  urine  it  must  first  be  converted  into  a 
soluble  salt  of  lead.      This  is  best  effected  by  giving  potas- 

'  Von  Jaksch,  "(!liiiical  Diagnosis,"  1897,  p.  375. 


METALLIC  SUBSTANCES.  185 

sium  iodide,  which  combines  with  the  lead,  forming  iodide 
of  lead,  and  is  ehminated  by  the  kidneys.  Even  after 
giving  potassium  iodide,  and  under  the  most  favorable 
conditions,  only  minute  traces  of  lead  are  eliminated  in 
twenty-four  hours.  Therefore,  a  large  quantity  of  urine 
is  required  for  the  analysis,  and  every  precaution  taken  to 
prevent  accidental  contamination. 

Analysis. — The  first  step  in  the  analysis  for  either  ar- 
senic or  lead  is  (i)  the  destruction  of  the  organic  matter  of 
the  urine,  and  the  addition  of  sulphuric  acid  for  the  purpose 
of  driving  off  the  nitric  acid,  thus  leaving  the  residue  in  the 
form  of  sulphates  ;  and  (2)  the  application  of  independent 
tests  for  either  lead  or  arsenic  as  the  case  may  be. 

/.  Destnictioji  of  Orgatiic  Matter. — Take  at  least  one 
liter  of  urine  in  an  evaporating  dish,  and  evaporate  to  dr)^- 
ness  over  a  water-bath.  Add  to  this  residue  about  100  c.c. 
of  concentrated  nitric  acid  (C.  P.),  and  continue  the  heat 
until  the  acid  has  evaporated,  when  a  yellow  cake  remains. 
Transfer  this  yellow  mass — nitrates  and  nitro-compounds — 
to  a  crucible  by  means  of  a  porcelain  spatula,  heat  with  a 
Bunsen  flame  until  the  mass  ignites,  and  continue  the  heat 
until  a  white  residue  remains.  Cool  ;  add  10  to  20  c.c.  of 
concentrated  sulphuric  acid  (C.  P.),  anti  heat  until  all  of  the 
nitric  acid  has  been  expelled — that  is,  until  the  red  fumes 
disappear  and  dense  white  fumes  are  evolved.  Cool,  and 
then  add  from  25  to  50  c.c.  of  distilled  water,  and  filter, 
reserving  the  filtrate  for  the  test  for  arsenic.  The  precipitate 
on  the  filter  is  washed  several  times  with  distilled  water  in 
order  to  remove  all  soluble  sulphates,  and  the  final  residue 
on  the  filter  reserved  for  the  test  for  lead. 

2.  {a)  Process  for  Arsenic. — The  filtrate  from  the  insolu- 
ble sulphates,  which  contains  any  arsenic  that  may  be 
present,  is  then  introduced  into  a  Marsh  apparatus  that  has 
been  previously  tested  and  found  to  be  free  from  arsenic. 
The  approximate  quantity  of  arsenic  can  be  judged  from  the 
intensity  of  the  mirror  of  metallic  arsenic  obtained  in  the 
delivery  tube,  and  should  be  expressed  in  hundredths  of  a 
milligram. 

Great  care  should  be  taken  to  expel  all  of  the  nitric  acid 
by  means  of  the  sulphuric  acid,  otherwise  an  explosion  will 
ensue  when  the  solution  is  put  into  the  Marsh  apparatus. 

(^)  Process  for  Lead. — The  residue  on  the  filter-paper, 
which   consists  of  insoluble   sulphates,  including    lead   sul- 


186  ABNORMAL  CONSTITUENTS  OF  URINE. 

phate,  is  thoroughly  extracted  with  hot  dilute  ammonium 
acetate  containing  an  excess  of  acetic  acid,  and  then  filtered. 
A  current  of  sulphureted  hydrogen  is  passed  through  the 
filtrate  for  about  an  hour,  the  lead  acetate  being  precipi- 
tated as  lead  sulphide.  Filter,  dissolve  the  residue  in  hot 
dilute  nitric  acid,  run  into  a  watch-glass,  and  evaporate  to 
dryness  over  a  water-bath.  A  preliminary  test  for  lead 
may  be  made  at  this  time,  by  drawing  through  the  residue 
a  drop  of  a  moderately  strong  solution  of  potassium 
iodide,  and  thoroughly  drying.  If  lead  be  present,  the 
yellow  iodide  of  lead  will  be  obtained.  ^  The  residue  on 
the  watch-glass  is  then  dissolved  in  hot  dilute  acetic  acid 
and  filtered.  The  filtrate,  which  contains  the  lead  in  the 
form  of  an  acetate,  is  then  treated  with  either  a  few  drops 
of  a  saturated  solution  of  potassium  chromate,  or  a  few 
cubic  centimeters  of  dilute  sulphuric  acid,  and  allowed  to 
stand  twenty-four  hours.  The  solution  that  contains  the 
lead  chromate  or  sulphate  is  then  filtered,  and  the  precipi- 
tate, which  is  usually  exceedingly  slight,  is  washed  a  few 
times  with  distilled  water.  Sulphureted-hydrogen  water, 
which  has  been  previously  filtered,  is  allowed  to  pass 
through  the  filter-paper  holding  the  precipitate,  and  the 
filter  then  carefully  dried.  If  lead  be  present,  a  slight  black 
precipitate  will  be  seen  adhering  to  the  surface  of  the  filter- 
paper  near  its  center. 

Mercury. — This  substance  appears  in  the  urine  follow- 
ing the  external  or  internal  use  of  its  various  compounds. 
The  test  is  applied  in  the  following  manner  : 

Acidulate  a  portion  of  the  urine  with  hydrochloric  acid, 
then  add  copper  filings,  and  heat  to  from  50°  to  60°  C.  for 
about  five  minutes  ;  let  stand  until  cool.  Wash  the  cop- 
per filings,  place  them  in  a  shallow  dish,  and  at  one  side  of 
the  dish,  or  on  a  watch-glass  that  is  to  be  inverted  over 
the  filings,  place  one  drop  of  a  i  per  cent,  solution  of  gold 
chloride ;  heat  over  a  low  flame.  The  mercuiy  that  is 
deposited  on  the  copper  will  be  volatilized  and  will  redden 
the  solution  of  gold  chloride.  According  to  Brugnatelli,^ 
this  test  is  capable  of  detecting  -^^  of  a  milligram  of  mer- 
cury in  one  liter  of  urine. 

Chloral. — A  simple  test  for  chloral  in  the  urine  is  the 

^  This  is  not  a  reliable  test,  as  a  trace  of  iron,  which  is  oftpn  present,  will 
give  the  same  reaction. 

^  "Journ.  de  Pharm.,"    April,  1890,  p.  367. 


HEMATOPORPHYRIN.  187 

so-called  isocyanplioiyl  test.  The  principle  of  the  test  de- 
pends upon  the  fact  that  an  alkali  decomposes  the  chloral 
into  formic  acid,  which  immediately  unites  with  the  alkali 
to  form  a  formiate  and  chloroform,  which  in  the  presence  of 
aniline  results  in  a  characteristic  volatile  compound. 

Test. — Take  one-third  of  a  test-tube  of  urine,  and  add 
one  drop  of  pure  aniline  (aniline  oil),  and  about  one  finger- 
breadth  of  an  alcoholic  solution  of  sodic  hydrate, — or  an 
equal  amount  of  a  strong  aqueous  solution  of  sodic  hydrate 
and  alcohol  may  be  used, — and  heat.  If  chloral  be  present, 
a  volatile  compound,  having  a  very  disagreeable  odor,  is 
evolved. 

In  many  instances  this  test  is  very  unsatisfactory  ;  it  is, 
therefore,  necessary  to  resort  to  other  more  complicated 
methods,  the  one  proposed  by  Duroy  ^  being  advised. 

Iodides  and  Bromides. — Iodides  and  bromides  make 
their  appearance  in  the  urine  after  their  administration.  The 
presence  of  iodides  is  frequently  observed  in  the  nitric  acid 
test  for  albumin.  Iodine  is  set  free  by  the  nitric  acid,  and 
appears  as  a  reddish-brown  color-zone  at  the  juncture  of  the 
urine  and  acid,  the  color  usually  becoming  gradually  diffused 
through  the  column  of  acid.  When  the  presence  of  an  iodide 
is  suspected,  the  following  test  may  be  readily  applied  : 

Test. — Take  one-half  test-tube  of  urine,  add  a  small 
amount  of  chloroform, — about  one  fingerbreadth, — then 
add  a  few  drops  of  yellow  nitric  acid,  and  shake.  The 
chloroform  takes  up  the  iodine,  which  is  set  free  by  the 
nitric  acid,  and  assumes  a  pink  or  purple-red  color. 

The  presence  of  bromides  is  determined  in  the  following 
manner  : 

'Test. — Proceed  exactly  as  in  the  test  for  iodine,  care 
being  taken  to  add  more  of  the  yellow  nitric  acid  than  in 
the  test  for  iodine,  in  order  to  completely  set  free  the 
bromine.  The  chloroform  takes  up  the  bromine,  and 
assumes  an  Indian-red  color — a  mixture  of  red,  yellow,  and 
brown. 

HEMATOPORPHYRIN. 

Hematoporphyrin,  CjgHj^NjOg,  is  a  coloring-matter  de- 
rived from  the  blood,  and  normally  present  in  the  urine, 
but  only  in  traces.      It  was  discovered  in    1871    by  Hoppe- 

1  WTiarton  and  Stille,  1884,  p.  395. 


188 


ABNORMAL  CONSTITUENTS  OF  URINE. 


Seyler,  who  found  that  by  treating  hematin  with  concen- 
trated sulphuric  acid  and  heating,  there  resulted  a  com- 
pound whose  acid  and  alkaline  solutions  showed  unusual 
spectral  bands.  To  this  new  compound  he  gave  the  name 
"  hematoporphyrin."  Since  its  discovery,  it  has  been  recog- 
nized by  a  number  of  observers  and  under  a  variety  of  cir- 
cumstances. 

Hematoporphyrin  is  identical  with  iron-free  hematin 
(Nencki).  A  urine  containing  this  coloring-matter,  when 
viewed  by  reflected  light,  is  opaque  and  almost  black  ;  or,  in 
a   thin    layer,   it    is   reddish-brown.       In  an   isolated   form 


m  m  m   m  no 


a  /3    \      ^-  (5"      I  ^        \ 

Fig-.  20. — Hematoporphyrin  spectra  ;   i,.\cid;  2,  alkaline;  5,  neutral. 


hematoporphyrin  is  nearly  insoluble  in  water,  in  dilute 
acetic  acid,  benzol,  and  nitrobenzol  ;  it  is  slightly  solu- 
ble in  ether,  chloroform,  and  amyl  alcohol,  and  readily 
soluble  in  alcohol,  alkaline  hydrates,  and  carbonates,  as 
well  as  in  dilute  mineral  acids. 

Spectra. — The  acid  alcoholic  solution  shows  (Fig.  20, 
i)  two  absorption  bands  :  one  rather  dark,  situated  between 
Frauenhofer's  lines  C  and  D,  with  its  right  border  over- 
lapping D ;  and  the  second,  sharpl}-  defined,  nearly  inter- 
mediate between  D  and  E. 

The  a/kaline  solution  presents  (Fig.  20,  2)  a  four -banded 


HEMATOPORPHA'RIN.  189 

spectrum  as  follows  :  A  faint  and  very  narrow  band  about 
midway  between  C  and  D ;  two  between  D  and  E,  one 
with  its  left  border  near  D,  the  other  including  E ;  the 
fourth  band,  which  is  the  darkest  of  all,  but  which,  how- 
ever, is  not  well  defined,  includes  nearly  all  of  the  space 
between  b  and  F,  and  incloses  F. 

The  neutral  and  victallic  spectra  are  represented  in  the 
accompanying  illustration  (Fig.  20,  3)  ;  they  are  less  char- 
acteristic than  the  acid  and  alkaline  spectra,  and  therefore 
will  not  be  described  here  in  detail. 

Clinical  Significance. — Since  urine  normally  contains 
traces  of  hematoporphyrin,  its  presence  becomes  of  im- 
portance only  when  it  is  present  in  large  amounts.  It  was 
first  discovered  in  the  urine  by  Baumstark  (1874)  in  a  case 
of  leprosy,  and  then  by  MacMunn,  le  Nobel,  and  others  in 
acute  articular  rheumatism.  Neusser  found  this  pigment 
in  cases  of  phthisis  pulmonalis,  and  pleurisy  with  effusion. 
Perhaps  its  most  frequent  appearance  in  large  amounts  is  fol- 
lowing the  prolonged  use  of  sulphonal,  trional,  or  tetronal ; 
it  is  only  rarely  found  after  one  or  two  doses  of  any  one 
of  these  three  drugs.  ^  It  is  conmionly  found  in  cases 
of  lead-poisoning,  of  which  Nakarai  has  reported  six  ;  the 
author  has  met  with  it  in  cases  of  lead-poisoning,  but 
never  in  large  quantities.  This  coloring-matter  has  also 
been  observed  in  cases  of  intestinal  tuberculosis  (Nakarai). 
The  bearing  of  nervous  phenomena  upon  the  production 
of  hematoporphyrin uria  is  a  subject  that  requires  further 
study.  In  two  cases  reported  by  Rankin  and  Partington 
and  one  by  the  author,  obscure  nervous  symptoms  were 
prominent,  and  possibly  had  some  bearing  on  the  cause  of 
the  hematoporphyrinuria. 

Salkowski's  Method  for  the  Separation  of  Hemato- 
porphyrin.—  "Take  about  30  c.c.  of  urine,  add  baryta 
mixture  (equal  parts  of  a  10  per  cent,  solution  of 
barium  chloride  and  a  saturated  solution  of  barium  hy- 
drate), until  it  is  completely  precipitated.  Wash  once  with 
water,  and  once  with  absolute  alcohol,  using  the  latter 
drop  by  drop.  Transfer  the  precipitate  to  an  evaporating 
dish,  add  from  6  to  8  drops  of  concentrated  hydrochloric 
acid  and  sufficient  absolute  alcohol  to  make  a  thin  pap, 
then  stir  thoroughly.     Heat  over  a  water-bath,  filter  through 

1  Ogden,  "  Boston  Medical  and  Surgical  Journal,"  Feb.  24,  1898. 


190  ABNORMAL  CONSTITUENTS  OF  URINE. 

a  dry  filter-paper,  and  finally  add  sufficient  absolute  al- 
cohol to  make  from  8  to  lo  c.c.  of  filtrate." 

This  solution  (acid)  may  be  examined  directly  with  the 
spectroscope  for  the  bands  of  acid  hematoporphyrin,  or  it 
may  be  rendered  alkaline,  preferably  with  amnionic  hy- 
drate, and  examined  for  the  characteristic  bands  of  alkaline 
hematoporphyrin. 

The  spectroscopic  examination  of  this  alcoholic  solution 
must  be  made  within  a  few  hours  after  its  preparation,  since 
the  solution  readily  decomposes,  after  which  it  is  useless 
for  observation. 

Detection. — This  coloring-matter  can  only  be  detected 
with  certainty  by  means  of 'the  spectroscope.  The  four 
spectral  bands  of  the  alkaline  solution  are  most  charac- 
teristic. 


MELANIN. 

Melanin  is  a  pigment  that  is  sometimes  found  in  the 
urine  of  persons  suffering  from  pigmented  tumors.  It  is 
usually  found  in  solution  in  the  urine,  and  more  rarely  in 
the  form  of  small  black  granules  which  are  in  suspension. 
Freshly  voided  urine  containing  melanin  is  usually  trans- 
parent and  of  a  normal  color.  When,  however,  the  urine 
is  allowed  to  stand  exposed  to  the  air,  the  color  changes  to 
a  brown,  and  finally  to  a  black.  Only  in  rare  instances  is 
the  urine  black  when  it  leaves  the  body. 

Melanin  is  eliminated  in  the  form  of  a  chromogen, — nicla- 
nogcn, — which  becomes  oxidized  in  the  air  or  by  oxidizing 
agents,  with  a  resulting  dark  or  black  color  due  to  a  de- 
posit of  the  pigment,  melanin.  Just  where  this  pigment 
is  converted  into  a  chromogen  in  the  body  has  not  yet  been 
determined.  Ganghofner  and  Pribram  claim  that  the  change 
takes  place  in  the  liver,  but  this  is  still  a  matter  of  doubt. 

Melanin  is  insoluble  in  water,  ether,  amyl  alcohol,  and 
dilute  acids.  It  is  readily  soluble  in  sodic  and  ammonic 
hydrates,  sodic  carbonate,  and  monosodic  phosphate  ;  hence 
it  is  not  precipitated  carbon.  It  contains  iron,  sulphur, 
and  nitrogen.  The  chromogen,  melanogen,  is  readily  oxi- 
dized by  potassium  bichromate  with  sulphuric  acid,  a  five 
per  cent,  solution  of  chromic  acid,  fuming  nitric  acid, 
potassium  permanganate,  and  potassium  chlorate  with 
hydrochloric  acid,  with  a   resulting  black  color. 


PTOMAINES  AND   LEUCOMAINES.  191 

Litten  observed  that  urine  containing  melanin  did  not 
undergo  ammoniacal  fermentation,  but,  instead,  became 
more  acid  than  normally  with  the  formation  of  a  thick 
fungus-growth  on  its  surface.  He  also  found  that  the 
urine  often  contained  a  reducing  substance  similar  to 
glucose  ;  such  a  reaction,  however,  has  not  been  reported 
by  other  observers. 

Clinical  Significance. — Melanuria  is  most  commonly 
seen  in  case  of  melanotic  sarcoma  in  some  part  of  the 
body,  not  necessarily  in  the  kidneys.  It  has,  very  rarely, 
been  observed  to  a  marked  degree  in  severe  wasting  dis- 
eases, and  has  also  been  observed  in  persons  suffering  from 
repeated  attacks  of  intermittent  fever.  The  urine  of  indi- 
viduals suffering  from  melanotic  new  growths  may  be  en- 
tirely free  from  melanin  while  the  growth  is  actively  pro- 
gressing. 

Detection. —  i.  The  most  sensitive  test  for  the  presence 
of  melanin  is  the  addition  of  bromine  water,  which  causes 
a  yellow  precipitate  that  gradually  blackens  (Zeller). 

2.  A  few  drops  of  a  fairly  concentrated  solution  of  ferric 
chloride  will  cause  the  urine  to  turn  gray :  if  more  be  added,  a 
precipitate  of  phosphates  falls,  carrying  the  coloring-matter 
with  it,  and  again  dissolves  with  an  excess  of  the  iron  solu- 
tion (v.  Jaksch,  Pollak). 

3.  Sodium  nitroprusside  with  caustic  potash  and  acetic 
acid  gives  a  deep-blue  color,  probably  due  to  the  formation 
of  soluble  and  insoluble  Prussian  blue  (v.  Jaksch).  This 
test,  however,  can  not  always  be  obtained  with  melanin 
that  has  been  isolated  from  the  urine,  and  the  reaction  must 
not  be  regarded  as  a  test  for  melanin,  or  only  when  other 
tests  have  shown  the  presence  of  melanin  or  melanogen. 

Morner  separated  the  coloring-matter  that  was  in  the 
form  of  a  chromogen  in  the  urine  by  precipitating  with 
baryta  water,  and  then  purifying. 

PTOMAINES  AND  LEUCOMAINES.— TOXICITY  OF  URINE. 

Ptomaines  may  be  defined  as  organic  chemic  com- 
pounds, basic  in  character,  and  formed  by  the  action  of 
bacteria  on  nitrogenous  matter.  On  account  of  their  basic 
properties,  in  which  they  resemble  the  vegetable  alkaloids, 
ptomaines  may  be  called  putrefactive  alkaloids.  They  have 
also  been  called  animal  alkaloids,  but  this  is  a  misnomer, 


192  ABNORMAL  CONSTITUENTS  OF  URINE. 

because,  in  the  first  place,  some  of  them  are  formed  in  the 
putrefaction  of  vegetable  matter,  and,  in  the  second  place, 
the  term  "  animal  alkaloids  "  is  more  properly  restricted 
to  the  leucomaines, — those  basic  substances  which  result 
from  tissue  metabolism  in  the  body. 

While  some  of  the  ptomaines  are  highly  poisonous,  this 
is  not  an  essential  property,  and  others  are  wholly  inert. 
Indeed,  the  greater  number  of  those  which  have  been  iso- 
lated up  to  the  present  time  do  not,  when  employed  in  single 
doses,  produce  any  apparent  harmful  effects.  Brieger  re- 
stricts the  term  ptomaine  to  the  nonpoisonous  basic  pro- 
ducts, and  designates  the  poisonous  ones  as  "toxines." 

Since  all  putrefaction  is  due  to  the  action  of  bacteria,  it 
follows  that  all  ptomaines  result  from  the  growth  of  these 
organisms.  The  kind  of  ptomaine  formed  will,  therefore, 
depend  upon  the  individual  bacterium  engaged  in  its  pro- 
duction, the  nature  of  the  material  being  acted  upon,  and 
the  conditions  under  which  the  putrefaction  goes  on,  such 
as  the  temperature,  the  amount  of  oxygen  present,  and  the 
duration  of  the  process. 

All  ptomaines  contain  nitrogen  as  an  essential  part  of 
their  basic  character.  In  this  they  resemble  the  vegetable 
alkaloids.  Some  of  them  contain  oxygen,  while  others  do 
not.  The  latter  correspond  to  the  volatile- vegetable  alka- 
loids, nicotine  and  coniine,  and  the  former  correspond  to 
the  fixed  alkaloids. 

It  was  formerly  supposed  that  putrefaction  was  simply 
oxidation,  but  the  researches  of  Pasteur  and  others  have 
demonstrated  the  fact  that  countless  myriads  of  minute 
organisms  are  engaged  constantly  in  transforming  matter 
from  organic  to  the  inorganic  form.  Hermetically  seal  the 
organic  matter  and  it  will  remain  unchanged  indefinitely. 

According  to  Pouchet,  healthy  urine  contains  traces  of 
certain  toxic  substances  of  an  alkaloidal  nature  ;  and  accord- 
ing to  the  researches  of  Bouchard,  Lepine,  and  Guerin, 
these  bodies  are  more  abundant  under  diseased  conditions. 
They  were  found  by  A.  Villiers  as  an  invariable  manifesta- 
tion in  measles,  diphtheria,  and  pneumonia.  Pouchet  found 
in  the  urine  of  cholera  an  alkaloid  which  was  not  identical 
with  that  observed  by  him  in  the  feces  of  the  same  disease. 
Feltz  found  similar  bodies  in  the  urine  of  cancer  patients, 
and  Lepine  in  that  of  pneumonia.  Toxines  have  been 
found  in  the  urine  of  scarlet  fever  and  pneumonia  (Albu) ;  in 


PTOMAINES.  193 

carcinoma  of  the  stomach,  and  in  Addison's  disease  (Ewald, 
Jacobsen).  Bouchard  discovered  that  human  urine  acted 
as  a  poison  when  injected  into  the  veins  of  a  rabbit,  and  he 
referred  the  toxic  effects  to  various  substances,  among  which 
were  animal  alkaloids. 

A.  B.  Griffiths  has  published  a  series  of  alkaloids  which 
he  has  isolated  from  the  urine  in  several  diseases.  They 
are  as  follows  : 

Parotitis. — CgHj^N^O^  (isomeric  with  lysatin),  white  prisms, 
soluble  in  water,  ether,  and  chloroform  ;  is  neutral,  and  has  a 
bitter  taste.  Gives  a  bright  yellow  precipitate  with  phospho- 
tungstic  acid,  a  white  precipitate  with  phosphomolybdic  acid, 
and  a  brown  precipitate  with  tannin.  On  boiling  with  mercuric 
oxide  it  furnishes,  first,  kreatin,  then  methylguanidin,  then 
oxalic  acid,  and  finally  the  base,  propylkreatin.  It  is  very 
poisonous,  producing  in  the  cat  excitement,  a  stoppage  of  the 
flow  of  saliva,  convulsions,  coma,  and  death,  ^ 

Scarlet  Fever. — C^H^^NO^,  a  white,  crystalline  substance, 
soluble  in  water  with  a  faint  alkaline  reaction.  It  gives  a 
crystalline  compound  with  chloral  hydrate  and  gold  chloride,  a 
yellowish-white  precipitate  with  phosphotungstic  acid,  a  white 
precipitate  with  phosphomolybdic  acid,  and  a  yellow  precipitate 
with  picric  acid.     It  is  also  precipitated  by  Nessler's  reagent.  ^ 

Diphtheria.  —  Gj^H^^N^Og,  a  white,  crystalline  substance 
which  gives  a  yellow  precipitate  with  tannin,  a  white  precipitate 
with  phosphomolybdic  acid,  and  a  yellow  precipitate  with 
Nessler's  reagent.  It  appears  in  cultures  of  the  diphtheria 
bacillus.^ 

Measles. — CjH.NjQ  (glycocyamidin),  in  the  form  of  white 
plates,  whose  solution  in  water  has  an  alkaline  reaction.  The 
compound  with  platinic  chloride  is  in  the  form  of  microscopic 
needles,  and  that  with  HgGl^,  nearly  insoluble  prismatic  needles. 
It  is  precipitated  by  picric,  phosphomolybdic,  and  phospho- 
tungstic acids.  It  is  very  poisonous  to  the  cat,  causing  fever 
and  death  in  about  thirty-six  hours.  ^ 

Pertussis. — Cj.HjgNO^,  a  white,  crystalline  substance,  soluble 
in  water,  and  forms  a  compound  with  chloral  hydrate,  and  one 
with  chloride  of  gold.  It  gives  a  white  precipitate  with  phos- 
phomolybdic acid,  a  yellow  precipitate  with  picric  acid,  and  a 
brown  precipitate  with  tannin.  It  also  appears  in  the  cultures 
of  the  pertussis  bacilli  of  Afanasieff. '' 

Glanders. — G,.HjgNjOg,  a  white,  crystalline  substance,  which 
is  soluble  in   water  and  has  an   alkaline  reaction.       The  pre- 

1  "Comptes  Reiidiis,"  cxiii,  656.  2  /_„,_  ^-//  3  /„,■   ,,/_ 

*  Loc.  cit.,  cxiv,  497,  1892.  5  j^g^^  ^-ji 

13 


194  ABNORMAL  CONSTITUENTS  OF  URINE. 

cipitates  with  chloral  hydrate,  chloride  of  gold,  and  chloride  of 
platinum  are  crystalline.  It  gives  a  greenish  precipitate  with 
phosphotungstic  acid,  a  brownish-white  precipitate  with  phos- 
phomolybdic  acid,  a  yellow  precipitate  with  picric  acid,  and 
is  precipitated  by  Nessler's  reagent.  It  also  appears  in  cul- 
tures of  the  bacilli  of  glanders.  When  it  is  injected  sub- 
cutaneously  into  a  rabbit,  it  causes  an  abscess  at  the  seat  of 
inoculation,  specific  nodes  in  the  lungs  and  spleen,  metastatic 
abscesses,  and  death.  ^ 

Pneumonia.  —  Cj^^Hj^N^O,,  in  the  form  of  white,  oblique 
prisms,  which  are  soluble  in  water  ;  its  solution  has  an  alkaline 
reaction.  It  gives  a  white  precipitate  with  phosphotungstic 
acid,  a  yellowish-white  precipitate  with  phosphomolybdic  acid, 
a  brownish  precipitate  with  Nessler's  reagent,  and  a  yellow  pre- 
cipitate with  picric  acid.  Its  solution  rotates  the  plane  of 
polarized  light  to  the  right  [aj^  =  23.  5°.  2 

Epilepsy. — Cj^H^jN^O,,  white,  oblique  prisms,  which  dis- 
solve in  water;  its  aqueous  solution  has  an  alkaline  reaction. 
The  precipitate  with  mercuric  chloride  is  greenish  white;  with 
silver  nitrate,  yellowish;  with  phosphotungstic  acid,  white; 
with  phosphomolybdic  acid,  brownish-white;  and  with  tannin, 
yellow.  When  injected  into  animals,  it  causes  tremor,  dilatation 
of  the  pupils,  convulsions,  and  death.'' 

Erysipelas. — CjjHjgNOj,  orthorhombic  plates,  which  are  sol- 
uble in  water.  It  gives  a  white  precipitate  with  HgCI^;  with 
ZnCljj,  a  granular  precipitate,  which,  upon  heating,  dissolves 
with  a  resulting  decomposition  ;  with  Nessler's  reagent  a  green 
])recipitate,  with  picric  acid  a  yellow  precipitate,  and  with  gold 
chloride,  a  yellow  precipitate,  which  is  soluble  in  water.  The 
compound  with  platinic  chloride  is  in  the  form  of  prismatic 
needles.  It  is  also  precipitated  by  phosphotungstic  and  phos- 
phomolybdic acids  and  tannin.  It  is  very  poisonous,  causing 
in  animals  high  fever,  and  death  in  about  eighteen  hours.* 

Puerperal  Eever. — C^^H^gNO^,  a  white,  crystalline  substance, 
soluble  in  water  and  with  an  alkaline  reaction.  It  gives  a 
red  precipitate  with  tannin,  a  yellow  precipitate  with  picric 
acid,  and  a  brownish-white  precipitate  with  phosphomolybdic 
acid.  It  is  also  precipitated  by  Nessler's  reagent.  It  is  very 
poisonous,  killing  a  dog  in  about  twelve  hours. '^ 

Eczema. — C^H,j.NO,  a  white,  crystalline  substance,  soluble 
in  water  and  with  an  alkaline  reaction.  The  compounds  with 
chloral  hydrate,  gold  chloride,  and  platinic  chloride  are  crystal- 
line. With  phosphotungstic  acid  it  gives  a  brownish  precipitate, 
with  phosphomolybdic  acid  a  yellow  precipitate,  with  picric  acid 

1  Loc.  lit.,  cxix,  1382.  1892.  2  /(,j-_  ^if^  3 1^0^^  cit.,  cxv,  185,  1892. 

■*  Loc.  cit.,  cxv,  667.  *  Loc.  cit.y  cxv,  668. 


PTOMAINES.  195 

a  yellow  precipitate,  with  AgNOj  a  yellowish  precipitate,  and 
with  HgClj  a  greenish  precipitate ;  it  is  also  precipitated  by 
Nessler's  reagent.  When  a  solution  of  this  substance  in  steril- 
ized water  is  injected  subcutaneously  into  a  rabbit,  it  causes  a 
marked  inflammation  at  the  point  of  inoculation,  high  fever,  and 
death. ^ 

Influenza.— CgYl^l<iO^,  white,  prismatic  needles,  which  have 
a  faintly  alkaline  reaction.  The  precipitate  with  phosphotungstic 
acid  is  brownish  ;  with  phosphomolybdic  acid,  yellowish  ;  with 
picric  acid,  yellow  ;  with  tannin,  red  ;  with  HgCl^,  white  ;  and 
with  Nessler's  reagent,  brown  ;  it  is  not  precipitated  by  ZnCl  . 
It  produces  a  high  fever,  and  death  in  eight  hours.  This 
ptomaine  differs  from  that  of  pneumonia.  2 

Carcinoma  of  the  Uterus. —Q^^O^,  a  white  substance  in 
the  form  of  microscopic  needles,  soluble  in  water  and  with 
an  alkaline  reaction.  It  gives  a  yellow  precipitate  with  phos- 
photungstic acid,  a  brownish  precipitate  with  phosphomolybdic 
acid,  a  red  precipitate  with  AgNOj,  a  gray  precipitate' with 
HgCl^,  and  a  brownish  precipitate  with  Nessler's  reagent.  It 
causes  fever,  and  death  in  three  hours.  ^    ' 

P/eur/t/s.—C.Up^.  When  precipitated  from  chloroform,  it 
appears  as  colorless,  right-angled  plates  with  two  axes;  when 
separated  from  hot  water,  it  is  in  the  form  of  feathery  aggrega- 
tions. With  Nessler's  reagent  it  gives  a  bright  yellow  precipi- 
tate, which,  upon  standing,  becomes  brownish,  while  the  solu- 
tion has  a  reddish  color.  This  precipitate  is  dissolved,  and  the 
solution  rendered  colorless  by  heat.  It  is  not  precipitated  by 
potassium  ferrocyanide  in  the  cold,  but  when  the  mixture  is 
heated,  it  gives  a  white  or  bright  yellow  precipitate,  which  be- 
comes green  upon  standing.  Ferric  chloride  gives  a  white  pre- 
cipitate ;  iodide  of  potassium  and  cadmium  a  red,  and  iodide 
of  potassium  and  bismuth  a  green  precipitate.  It  is  poisonous.  * 
Angina  Pectoris.  —  Cjj,HgNO^.  A  white  crvstalline  sub- 
stance, soluble  in  water,  and  faintly  alkaline!  It  gives  a 
yellowish  precipitate  with  phosphotungstic  acid;  a  yellow  pre- 
cipitate with  phosphomolybdic  acid  ;  a  red  precipitate  with 
tannin;  a  green  precipitate  with  AgNOg ,  a  green  precipitate 
with  HgCl^ ;  and  a  brown  precipitate  with  Nessler's  reagent. 
It  causes  fever,  and  death  in  two  hours.  •' 

The  experiments  of  Albu  «  have,  in  many  in.stances.  con- 
firmed  tho.sc    of    Griffiths.     Albu    found    alkaloids    in    the 

J  Loc.  cit.,  ex VI.  1205,  1893.  1  Loc.  at.,  cxvii,  744,  1893. 

^  Loc.  cit.,  cxviii,  1350,  1894. 

*"Chem.  News,"  lxx,  109;    "  Chem.  Centralbl.,"   1894,  11.  icx)0. 

*  '^Comptes  Rendus,"  cxx,  1128,  1895. 

8  A.  Albu,  "  Berliner  klin.    Wochenschr.,"  xxi,  8  u.   1081,  1894. 


196  ABNORMAL  CONSTITUENTS  OF  URINE. 

urine  of  cases  of  scarlet  fever,  measles,  pneumonia,  diph- 
theria, phthisis  with  hectic  fever,  sepsis  accompanying  car- 
cinoma of  the  uterus,  erysipelas,  Basedow's  disease,  tetanus, 
pernicious  anemia,  autointoxication  with  urticaria  following 
acute  gastric  catarrh,  and  in  diabetic  coma. 

Leucomaines  are  those  basic  substances  which  arc  found 
in  the  living  tissues,  either  as  the  products  of  fermentative 
changes  other  than  those  of  bacteria,  or  of  retrograde 
metamorphosis.  The  first  attempt  at  the  systematic  study 
and  generalization  of  these  basic  substances  was  made  by 
Gautier,  who  included  under  this  subject  all  of  those 
substances  which  are  formed  in  animal  tissues  during 
normal  life,  in  contradistinction  to  the  ptomaines  or  basic 
products  of  putrefaction.  The  distinction  between  vege- 
table and  animal  alkaloids  is  not  well  defined.  Vegetable 
tissues  are  known  to  contain  not  only  what  are  ordinarily 
designated  as  ptomaines,  such  as  choline,  but  also  leuco- 
maines, such  as  hypoxanthin,  xanthin,  etc.  Under  this  head 
must  also  be  placed,  on  account  of  their  relationship  to 
xanthin,  those  well-defined  alkaloidal  bases,  caffein  and 
theobromin. 

The  leucomaines  proper  may  be  divided  into  two  distinct 
and  well-defined  groups — (i)  the  uric  acid  group,  and  (2) 
the  kreatinin  group. 

The  first  of  these  groups  contains  a  number  of  well- 
known  bases,  w'hich  are  closely  related  to  uric  acid.  They 
are  as  follows :  Adenin,  hypoxanthin,  guanin,  xanthin, 
(uric  acid),  heteroxanthin,  methylxanthin,  paraxanthin, 
carnin,  episarkin,  pseudoxanthin,  cytosin,  gerontin,  sper- 
min. 

The  members  of  the  kreatinin  group  have  all  been  dis- 
covered by  Gautier,  and  by  him  are  regarded  as  allied  to 
kreatin  and  kreatinin.  They  are  as  follows  :  Kreatinin  and 
kreatin,  crusokreatinin,  xanthokreatinin,  amphikreatin,  and 
two  unknown  bases. 

Toxicity  of  Urine. — The  question  of  the  toxicity  of 
normal  urine  has  been  the  subject  of  much  controversy. 
From  the  experiments  of  Feltz  and  Ritter,  Astaschewsky, 
Schiffer,  Bouchard,  Lepine,  Stadthagen,  Gautier,  Guinard, 
and  others,  it  can  now  be  positively  stated  that  normal 
urine  does  possess  a  certain  degree  of  toxicity.  It  is  more 
difficult  to  decide  upon  the  nature  of  this  poison. 

Feltz    and    Ritter,    and,    independenth',    Astaschewsky, 


TOXICITY  OF  URINE.  197 

arrived  at  the  opinion  that  the  toxicity  was  chiefly  due  to 
the  potassium  salts  of  the  urine.  Although  Schiffer  ac- 
knowledged the  presence  and  action  of  the  inorganic  salts, 
he  maintained  that  the  urine  contained  a  definite  organic 
poison  for  the  reason  that  the  concentrated  aqueous  solu- 
tions from  alcoholic  extracts  of  the  urine-residue  killed 
large  rabbits  in  doses  corresponding  to  from  i  to  i  }4  liters 
of  urine  deprived  of  inorganic  salts. 

Bouchard  has  shown  that  from  30  to  60  c.c.  of  normal 
urine,  injected  intravenously,  will  kill  a  rabbit  weighing  one 
kilogram.  Hence  a  man  weighing  60  kilograms,  and  ex- 
creting 1200  c.c.  per  diem,  would,  if  50  c.c.  are  necessary 
to  kill  one  kilogram  of  living  matter,  secrete  enough  poison 
to  kill  24  kilograms  of  animal.  Bouchard  claims  that 
there  are  five  different  poisons  that  may  be  met  with  in  the 
urine,  each  one  of  which  produces  a  definite  symptom  : 
viz.,  narcosis,  salivation,  mydriasis,  paralysis,  and  convul- 
sions. He  found  that  the  day-urine,  which  is  chiefly  nar- 
cotic, is  from  two  to  four  times  more  toxic  than  that 
secreted  during  sleep,  and  that  the  latter  induces  convulsions 
and  is  antagonistic  to  the  former.  Further,  that  the  toxicity 
is  independent  of  the  density,  since  night-urine  is  denser 
than  that  secreted  during  the  day.  Bouchard  also  claims 
that  the  greater  part  of  the  toxicity  of  urine  is  due  to 
organic  poisons,  especially  to  coloring-matters  ;  and  that  the 
potassium  salts  are  regarded  as  the  cause  of  only  a  small 
fraction  of  the  toxicit^^ 

Lepine  also  found  that  about  60  c.c.  of  urine  were  suffi- 
cient to  kill  I  kilogram  of  animal.  To  the  inorganic  salts, 
however,  he  ascribed  a  much  greater  importance,  inasmuch  as 
he  estimates  that  85  per  cent,  of  the  intoxication  is  due  to 
this  cause.  Stadthagen  has  also  arrived  at  practically  the 
same  conclusion,  that  from  80  to  85  per  cent,  of  the  tox- 
icity^ is  due  to  the  inorganic  constituents.  A  part  of  the 
toxic  matter — i  5  to  20  per  cent. — is  therefore  due  to  organic 
substances.  No  one  organic  substance  in  the  urine,  such 
as  urea,  kreatin,  kreatinin,  etc.,  possesses  this  toxicit)^ 

It  is  now  a  well-established  fact  that  the  urine  of  certain 
infectious  diseases,  such  as  cholera  (Bouchard)  and  septi- 
cemia (Feltz),  is  far  more  poisonous  than  normal  urine. 
That  the  poisons,  basic  or  otherwise,  which  are  generated 
within  the  body  by  the  activity,  of  bacteria  can  be  excreted 
in  the  urine  is  seen  in  the  fact  that  immunitv  to  the  action 


198  ABNORMAL  CONSTITUENTS  OF  URINE. 

of  bacillus  pyocyaneus  has  been  conferred  on  animals  by 
previous  injection  of  urine  taken  from  animals  inoculated 
with  that  bacillus  (Bouchard),  or  with  filtered  cultures  of 
the  same  (Charrin  and  Ruffer). 

Furthermore,  the  excretion  of  the  tetanus  and  diphtheria 
poisons  by  the  urine  has  been  shown  to  take  place.  Thus, 
Brunner  demonstrated  the  tetanus  poison  in  the  urine  of 
experimental  animals,  but  failed  with  the  urine  of  the  dis- 
ease in  man.  Bruschettini,  however,  with  the  urine  of  a 
tetanus  patient,  produced  tetanic  symptoms  in  mice  by  the 
injection  of  from  3  to  10  c.c.  subcutaneously.  In  the  urine 
from  diphtheria  patients  Roux  and  Yersin  demonstrated  the 
presence  of  the  diphtheritic  poison  by  inducing  paralysis  in 
animals.  Although  basic  substances  are  not  present  in  the 
urine  of  cholera,  they  are  present  in  the  intestinal  discharges 
(putrescin  in  only  one  of  four  cases — Roos).  From  cholera 
feces  Pouchet  extracted  an  oily  fluid  very  poisonous  to 
frogs  ;  whereas  Villiers  obtained  a  base  which  produced 
convulsions  in  guinea-pigs. 

In  the  consideration  of  the  toxines  in  the  urine  of  infec- 
tious diseases  it  must  not  be  forgotten,  as  pointed  out  by 
Jawein,  that  the  poison  as  well  as  the  specific  germ  may  be 
present  in  the  urine.  Thus,  in  rabbits  that  died  as  a  result 
of  infection  with  anthrax  bacillus,  erysipelas  streptococcus, 
Eberth's  bacillus,  and  Frankel's  diplococcus,  the  urine 
was  found  to  contain  these  organisms. 


CHAPTER  VI. 


URINARY  SEDIMENTS. 


It  has  already  been  stated  that  strictly  normal,  freshly 
passed  urine  of  acid  reaction  contains  no  sediment  except 
faint  flocculi  of  mucus,  which  gradually  subside  toward 
the  bottom,  and  entangle  a  few  mucus-corpuscles  and  an 
occasional  epithelial  cell.  Should  the  urine,  however,  be 
alkaline,  as  is  frequently  the  case  three  or  four  hours  after 
a  meal,  it  may  be  more  or  less  cloudy  at  the  moment  it  is 
passed,  and  quickly  deposit  a  flocculent  precipitate  of  earthy 
phosphates,  which  may  occupy  considerable  bulk.  Upon 
microscopic  examination  the  sediment  will  be  found  to  con- 
sist of  amorphous  granules,  which  will  quickly  disappear  on 
the  addition  of  a  few  drops  of  acetic  acid. 

When  a  normal  urine  without  sediment  has  stood  for 
some  time,  especially  at  a  moderate  or  low  temperature, 
there  is  frequently  observed  a  deposit  of  amorphous  gran- 
ular matter,  usually  of  a  pink  color,  and  sometimes  it  is 
almost  colorless.  It  is  readily  soluble  by  heat,^  and  is 
composed  of  amorphous  urates — a  mixture  in  varying  pro- 
portions of  acid  urates  of  potassium,  sodium,  and  ammo- 
nium, with  which  urates  of  calcium  and  magnesium  are 
occasionally  commingled.  Such  a  deposit  of  urates  may 
also  contain  crystals  of  uric  acid  or  octahedral  crystals  of 
calcium  oxalate.  Bacteria  from  the  air  and  other  sources 
frequently  make  their  appearance  in  the  sediment ;  also, 
often,  spores  of  torula  cerevisiae — the  yeast  fungus — and 
spores  of  penicillium  glaucum  are  found. 

When  a  urine  becomes  alkaline  as  a  result  of  the  de- 
composition of  the  urea  into  ammonium  carbonate,  it  has 
an  entirely  different  appearance,  and  it  is  at  this  time  that 
we  find  myriads  of  bacteria,  together  with  a  deposit  of 
phosphates,  both  amorphous  and  crystalline.  At  the  very 
beginning   of  the   reaction,   when    the    urine   may  still  be 

199 


200  URINARY  SEDIMENTS. 

neutral  or  even  faintly  alkaline,  any  crystals  of  uric  acid  that 
may  be  present  begin  to  dissolve  and  to  change  their  form 
so  as  to  become  more  or  less  unrecognizable,  while  on  their 
fragments  may  often  be  seen  to  adhere  prismatic  crystals  of 
urate  of  sodium  and  dark  spheres  of  urate  of  ammonium. 
As  the  reaction  becomes  more  strongly  alkaline  the  uric 
acid  disappears  altogether,  and  the  field  becomes  crowded 
with  granules  of  amorphous  phosphate  of  lime,  beautiful 
triangular  prisms  ("  coffin-lid  "  shaped  crystals)  and  irregu- 
larly shaped  crystals  of  ammonio-magnesium  phosphate, 
and  the  dark  spheres  of  urate  of  ammonium  which  are  often 
beset  with  spiculae.     (Fig.  28.) 

The  methods  used  for  the  examination  of  urinary  sedi- 
ments are  both  microscopic  and  chemic.  By  means  of  the 
microscope  various  deposits  are  recognized  by  characteris- 
tics that  are  in  themselves  diagnostic.  But  the  micro- 
scope does  not  in  all  instances  reveal  the  exact  nature  of 
certain  substances,  and  then  it  becomes  necessary  to  resort 
to  chemic  tests,  which,  together  with  the  microscope,  afford 
reliable  data  concerning  the  substances  examined. 


METHODS  OF  OBTAINING  URINARY  SEDIMENTS. 

Two  methods  are  in  common  use  for  obtaining  urinary 
sediments — /.  e.,  {a)  centrifugal  victJwd  and  {Ji)  gravity 
mctliod. 

(a)  Centrifugal  Method. — More  recent  experience  has 
demonstrated  the  immense  advantages  of  the  centrifugal 
method  of  obtaining  urinary  sediments  for  purposes  of 
microscopic  examination.  The  principle  of  this  method  de- 
pends upon  the  fact  that  when  the  urine  is  placed  in  tubes 
and  revolved  at  a  high  speed  upon  horizontal  rotating  arms, 
a  centrifugal  force  is  exerted  upon  all  solid  particles  in  the 
urine,  hundreds  of  times  greater  than  gravity,  and,  conse- 
quently, the  urinary  sediment  is  deposited  in  the  bottom  of 
the  tubes  almost  immediately,  irrespective  of  the  specific 
gravity  of  the  urine  or  the  character  of  the  sediment. 
Some  of  the  advantages  of  this  method  are  as  follows  : 

1.  Centrifugal  sedimentation  of  the  urine  permits  of  an 
immediate  microscopic  examination,  instead  of  waiting  for 
from  twelve  to  twenty-four  hours  as  by  the  old  method  of 
gravity. 

2.  The  centrifugal  method  secures  more  completely  con- 


CENTRIFUGAL  METHOD. 


201 


centrated  sedimentation,  and,  therefore,  it  is   better  suited 
for  purposes  of  microscopic  diagnosis. 

3.  Microscopic  examination  of  freshly  voided  urine  may- 
be made  before  casts  or  morphologic  elements  have  had 
time  to  undergo  maceration  or  solution  in  the  urine,  and 
before  the  appearance  of  large  numbers  of  bacteria,  which 
always  greatly  obscure  the  microscopic  field. 

4.  It  affords  the  only  positive  means  of  distinguishing 
between  primary  and  secondary  crystalline  elements  in 
the    urine,   since  by   this   method   only   can  the   urine    be 


Fig.  21. — The  Purdy  electric  centrifuge. 


examined  microscopically  as  soon  as  voided,  and,  there- 
fore, before  the  formation  of  those  crystals  that  are  de- 
posited in  nearly  all  normal  urines  that  are  left  standing 
for  several  hours. 

5.  By  the  old  method  of  gravity,  it  sometimes  happens 
with  urines  of  high  specific  gravity  that  the  lighter  casts 
(such  as  those  of  the  narrow,  hyaline  order)  fail  to  settle, 
and  thus  elude  detection.  The  centrifuge  precipitates  all 
casts  without  delay,  irrespective  of  the  above-named  condi- 
tions. 


202 


URINARY  SEDIMENTS. 


It  will,  therefore,  be  readily  seen  that  the  centrifuge  is 
destined  to  supersede  the  old  method  of  gravitation  for  all 
purposes  of  urinary  sedimentation. 

Of  the  various  number  of  centrifugal  machines  on  the 
market  the  electric  centrifuge  devised  by  Dr.  Purdy,  of 
Chicago,  is  undoubtedly  the  most  serviceable. 

The  Purdy  electric  cenfrifnjj^e,'^  shown  in  figure  21,  can 
be  operated  on  the  interrupted  incandescent  illuminating 
current,  on  the  constant  illuminating  current,  on  the  storage 


c.c.\ 


Fig.  22. — Tubes  for  the  Purdy  centrifuge  :  a,  Percentage  tube ;  b,  sediment  tube. 


current,  and  on  the  galvanic  current  (sulphuric  cell) ;  and 
is  suitably  adjusted  for  operation  at  any  voltage  from  10  to 
120  volts,  providing  the  nature  and  strength  of  the  current 
be  specified. 

The  apparatus  is  capable  of  all  grades  of  speed  from  500 
to  10,000  revolutions  per  minute,  according  to  the  strength 
of  the  current  used  and  the  resistance  of  the  arm.  When 
the  sediment  tubes  (Fig.   22),  each  with  a  capacity  of  15 

^  The  Purdy  electric  centrifuge  is  manufactured  by  Williams,  Brown  and 
Earle,  918  Chestnut  St.,  Philadelphia. 


CENTRIFUGAL  METHOD. 


203 


c.c,  are  filled  and  introduced  into  the  aluminium  shields  of 
the  apparatus,  it  is  capable  of  sustaining  a  speed  of  from 
2000  to  2500  revolutions  per  minute,  the  tips  of  the  tubes 
at  the  same  time  describing  a  circle,  the  diameter  of  which 
is  13^  inches.  The  centrifugal  force  is  from  two  to  three 
thousand  times  greater  than  gravity,  so  that  all  the  elements 
of  a  sediment — organized  and  nonorganized — are  in  from 
three  to  five  minutes  forced  to  the  extreme  tips  of  the  tubes, 
where  they  may  at  once  be  utilized  for  microscopic  purposes. 
Concerning  the  Jiand  centrifuge,  of  which  there  are  a  large 


1/ 


Fig.  23. — The  Bausch  and  Lomb  spiral-gear  urinary  centrifuge  with  tubes  (one-fourth 

actual  size). 


number  on  the  market,  it  is  to  be  said  that  only  a  compara- 
tively {q.v^  are  of  practical  value.  The  spiral-gear'  centri- 
fuge, manufactured  by  The  Bausch  &  Lomb  Optical  Co., 
of  Rochester,  N.  Y.,  has  been  extensively  used  by  the 
author,  and  can  be  highly  recommended. 

The  centrifuge  proper  (Fig.  23)  consists  of  a  small  circu- 
lar case  containing  a  train  of  gears  made  of  extra  hardened 
bronze,  and  having  teeth  spirally  cut,  three  of  which  are 
engaged  at  all  times.      This  form  of  gearing  runs  easier  and 


204 


URINARY  SEDIMENTS, 


is  more  durable  than  any  of  the  straight  gear  machines,  as 
it  prevents  backlash  or  lost  motion.  The  centrifuge  is  very- 
small,  yet  it  is  strong  and  capable  of  a  high  rate  of  speed — 
3000  revolutions  per  minute. 

The  glass  tubes  used  for  holding  the  urine  are  both  gradu- 
ated and  plain,  and  have  practically  the  same  shape  as 
those    already   described   in    connection   with    the    electric 

centrifuge.  These  tubes  are  car- 
ried in  aluminium  shields,  and  are 
supported  on  elastic  cushions  to 
prevent  breakage  during  rotation. 
(b)  Gravity  Method.— The  old 
so-called  gravity  method  of  obtain- 
ing a  sediment,  and  one  that  is  not 
without  advantages  at  the  present 
time,  consists  in  placing  the  urine 
in  a  urine  glass  (Fig.  24)  having 
parallel  sides  and  a  concave- bot- 
tom, ^  then  covering  with  a  piece  of 
filter-paper,  a  glass  plate,  or  other 
convenient  article,  in  order  to  keep 
out  dust  and  other  foreign  matter. 
Allow  the  glass  to  stand,  prefer- 
ably in  a  dark  and  moderately  cool 
place,  until  the  urine  is  well  settled. 
The  time  required  for  a  sediment 
that  is  suitable  for  microscopic  ex- 
amination is  from  one  to  twenty- 
four  hours  ;  usually  a  satisfactory 
sediment  is  obtained  within  twelve 
hours.  Occasionally,  in  a  normal 
urine  or  one  of  high  specific  grav- 
ity, the  sediment  does  not  fall  to 
the  bottom  of  the  glass,  but,  instead,  is  suspended  in  the 
column  of  urine ;  this  cloud  is  sometimes  termed  the 
"  nubecula." 

The  chief  objection  to  the  use  of  this  method  is  the 
length  of  time  required  for  the  urine  to  settle.     Further- 


Fig.  24. — Urine  or  sediment 
glass. 


^  The  urine  glass,  also  sometimes  termed  sediment  glass,  should  be  made 
of  perfectly  clear,  smooth  glass  which  is  free  from  air-bubbles.  The  bottom 
of  the  glass  should  be  concave  and  without  the  objectionable  upward,  nipple- 
like projection  so  often  found  in  the  ordinary  sediment  glass.  These  glasses 
can  be  obtained  of  The  Richard  Briggs  Co.,  287  Washington  Street,  Boston. 


GRAVITY  METHOD. 


205 


more,  unless  preservatives  are  used,  the  urine  often  un- 
dergoes alkaline  decomposition  before  a  sediment  settles, 
when  it  becomes  unfit  for  microscopic  examination.  But 
preservatives  may  be  used  without  altering  the  sediment  or 
otherwise  interfering  with  the  microscopic  examination. 
Whenever  this  method  is  used,  it  is  the  habit  of  the  writer 
to  add  to  that  portion  of  the  urine  that  is  set  aside  for 
sediment  from  15  to  30  c.c.  of  a  saturated 
(4  per  cent.)  solution  of  boric  acid,  which, 
under  ordinary  conditions,  preserves  the 
urine  until  the  sediment  is  satisfactorily 
settled.  A  drop  or  two  oi  formalin  (for- 
maldehyde gas  in  water)  may  be  added  to 
the  urine,  but  not  always  with  satisfactory 
results,  since  a  peculiar  crystalline  (?)  pre- 
cipitate is  often  deposited,  especially  if  too 
much  is  added,  which  seriously  interferes 
with  the  examination  of  the  sediment. 
Other  preservatives,  such  as  chloral,  sali- 
cylic acid,  chloroform,  etc.,  may  be  used, 
but  with  even  less  satisfactory  results. 

There  can  be  no  question  of  the  many 
advantages  of  the  centrifugal  method  over 
the  gravity  method  for  obtaining  sediments, 
and  the  writer  strongly  recommends  its  use 
for  both  the  practitioner  and  the  student. 
There  are,  however,  two  disadvantages  : 
viz.,  (i)  by  the  use  of  the  centrifuge  the 
proportion  of  abnormal  elements,  such  as 
casts,  blood  globules,  pus-corpuscles,  etc., 
may  be  very  large,  since  the  greater  part  ot 
the  sediment  is  included  in  a  drop  or  two 
of  fluid,  whereas  the  sediment  obtained  by 
gravity  might  really  contain  very  few  ab- 
normal elements  ;  the  examiner  is  thereby 
misled  as  to  the  extent  of  the  pathologic 
process.  This  is  particularly  the  case  in  judging  of  the 
amount  of  pus  which  a  given  urine  contains,  also  the  pro- 
portion of  crystalline  elements  in  a  urine.  (2)  The  drop  or 
two  of  sediment  obtained  by  the  use  of  the  centrifuge  may 
contain  so  much  pus,  so  many  crystals,  or  epithelial  cells 
as  to  obscure  any  renal  casts  that  would  otherwise  be 
readily  detected  in  a  sediment  obtained  by  gravity. 


Fig.  25. — Pipette  for 
sediments. 


206  URINARY  SEDIMENTS. 


THE  PREPARATION  OF  SEDIMENTS  FOR  MICROSCOPIC 
EXAMINATION. 

Having  obtained  a  well-settled  sediment,  either  by  the 
use  of  the  centrifuge  or  by  allowing  the  urine  to  stand  in  a 
urine  glass  to  settle  by  gravity,  the  examiner  should  supply 
himself  with  a  suitable  pipette,  slides,  and  cover-glasses, 
and  a  microscope  of  the  best  make. 

1.  Pipette. — Great  care  should  be  used  in  making  a 
pipette,  for  unless  the  drawn-out  tip  is  of  the  proper  shape 
and  the  opening  of  the  proper  size,  a  suitable  sediment  can 
not  be  obtained.  The  pipette  shown  in  figure  25  repre- 
sents the  approximate  size  of  the  glass  tubing  that  should 
be  used,  and  the  shape  of  the  drawn-out,  or,  what  may  be 
termed  the  proximal,  end.  If  the  proximal  tip  be  abruptly 
drawn  to  nearly  a  point,  and  the  opening  be  too  small,  a 
good  sediment  can  not  be  obtained.  The  other  end,  or 
distal  end,  of  the  glass  tube  should  be  rounded  off  in  the 
flame  so  as  to  prevent  cutting  the  finger,  and  the  opening 
should   be   nearly  as  large   as   the  diameter  of  the  tubing. 

2.  Slides  and  Cover-glasses. — These  should  be  free 
from  scratches  and  be  perfectly  clean.  The  No.  2  square  or 
oval  cover-glass  is  perhaps  best  suited  for  the  examination 
of  urinary  sediments. 

3.  Microscope. — It  will  not  be  necessary  here  to  give  a 
detailed  description  of  the  microscope  or  to  refer  to  its  use. 
The  instrument  should  be  one  of  the  best :  viz.,  the  Leitz 
or  Zeiss  microscope  made  in  Germany,  or  the  Bausch  & 
Lomb  microscope  made  by  the  Bausch  &  Lomb  Optical 
Co.,  of  Rochester,  N.  Y.  For  the  examination  of  urinary 
sediments  the  Abbe  condenser  can  not  be  satisfactorily 
used,  since  too  much  light  is  furnished  thereby,  the  ordinary 
diaphragm  supplied  with  each  instrument  being  most  ser- 
viceable. 

Method. — The  pipette,  held  between  the  thumb  and 
middle  and  ring-fingers,  is  carried  to  the  bottom  of  the 
sediment  glass  with  the  index-finger  (which  should  be  per- 
fectly dry)  pressed  upon  the  distal  end.  When  the  pipette 
has  reached  the  heaviest  portion  of  the  sediment,  it  is  gently 
rotated  between  the  thumb  and  fingers  without  removing 
the  index-finger  from  the  distal  end,  and  a  small  amount  of 
the  sediment  allowed  to  enter  slowly.  The  pipette  is  with- 
drawn from  the  urine  and  carefully  zviped  from  end  to  end 


CLASSIFICATION   OF   SEDIMENTS. 


207 


to  remove  all  fluid  from  its  outer  surface.  Two  or  three 
slides  are  then  placed  on  the  table,  and  a  drop  of  the  sedi- 
ment placed  on  each  and  covered  with  the  cover-glasses. 
The  preparations  are  then  ready  for  microscopic  examina- 
tion. The  writer,  who  uses  a  Leitz  microscope,  is  in  the 
habit  of  examining  the  specimen  first  with  a  low  power, — 
No.  5  objective  and  No.  i  eye-piece, — and  then  with  a 
higher  power — 7  objective  and  i  or  3  eye-piece.  Having 
carefully  searched  the  three  preparations,  it  is  probable  that 
most  or  all  of  the  elements  have  been  seen. 

It'  is  sometimes  necessary,  especially  if  the  sediment  is 
bulky,  to  first  take  a  sediment  from  the  upper  layer,  and 
then  one  from  the  bottom  layer,  in  order  to  be  able  to 
detect  the  lighter  elements  (casts,  etc.)  and  the  heavier  sub- 
stances (crystals). 

It  sometimes  happens  that  casts  and  cells  do  not  settle, 
but  are  held  in  suspension  in  a  cloud  near  the  top  of  the  col- 
umn of  urine.  When  such  a  cloud  is  present,  a  drop  of 
sediment  from  it  should  alwa\'s  be  examined. 


URINARY  SEDIMENTS. 

The  urinary  sediments  are  best  classified,  for  the  purpose 
of  study,  into  two  groups — i.  e.,  nonorganized  or  chemic, 
and  organized  or  anatomic  deposits,  as  follows  : 

I.  NONORClAMZEl). 


I. 

Uric  acid 

(cr\-stalline). 

2. 

Urates 

(amorphous  or  crystalline). 

3- 

Hippuric  acid 

(crystalline). 

4- 

Calcium  oxalate 

(crystalline). 

5- 

Calcium  phosphate 

(amorphous  or  crystalline). 

6. 

Ammonio-magnesium 

phosphate — triple    phosphate 
(cr}^stalline  or  amorphous). 

7- 

Calcium  carbonate 

(crystalline  or  amorphous). 

8. 

Cystin 

(cry.stalline). 

9- 

Cholesterin 

(crj'stalline). 

10. 

Leucin 

(crystalline). 

II. 

Tyrosin 

(crystalline). 

12. 

Hematoidin — bilirubin 

(crystalline). 

13- 

Xanthin 

(crystalline  or  amorphous). 

14. 

Indigo 

(crystalline). 

208  URINARY   SEDIMENTS. 


II.   ORGANIZED. 

I. 

Epithelium. 

2. 

Nucleo-albumin  (mucin). 

3- 

Blood. 

4- 

Pus. 

5- 

Renal  casts. 

6. 

Spermatozoa. 

7- 

Fat. 

8. 

Fibrin. 

9.    Fungi  and  infusoria. 

10.  Morbid  growths. 

1 1 .  Parasites. 


III.   EXTRANEOUS   SUBSTANCES. 


NONORGANIZED  SEDIMENTS. 

The  nonorganized  or  chemic  sediments  of  the  urine  are 
usually  crystalline,  although  in  a  few  instances  they  are 
amorphous,  and  are  to  be  distinguished  from  the  organized 
sediments  described  under  a  separate  heading. 

Uric  Acid.i — Uric  acid  crystals  are  frequently  found  as 
constituents  of  the  urinary  sediment.  They  always  occur 
in  an  acid  urine,  and  usually  in  one  that  is  strongly  acid. 
They  appear  in  normal  as  well  as  in  pathologic  urine.  The 
crystals  are  usually  colored  a  deep  yellow  or  orange-red, 
sometimes  a  pale  yellow,  and  sometimes  brown,  and  occa- 
sionally they  are  colorless.  Pure  uric  acid  is  very  difficultly 
ciystallizable  ;  therefore,  the  crystals  of  uric  acid  found  in 
the  sediment  are  those  of  the  impure  acid. 

Uric  acid  crystallizes  in  a  variety  of  shapes,  but  the 
typical  shape  may  be  said  to  be  the  rhombic  plate.  It  is, 
however,  comparatively  rare  to  find  these  typical  forms  in 
the  sediment,  the  great  majority  of  the  ciystals  found  being 
modifications  of  this  form.  (Fig.  26.)  Thus  we  find  the 
rectangular  prisms,  the  barrel,  whetstone,  club,  spear, 
wedge,  dumb-bell,  and  diamond  shapes  ;  also  the  crystal 
resembling  a  comb  with  teeth  on  two  sides,  the  rosette 
(coalescence  of  crystals  of  varying  shapes)  and  irregularly 
shaped  crystals,  all  of  which  have  a  more  or  less  yellow 
color,  except  the  diamond  form,  which  is  not  infrequently 

1  For  General  Consideration,  Properties,  and  Tests  for  Uric  Acid  see  pages 
59  to  71. 


URIC   ACID. 


209 


nearly  colorless.  There  are  many  more  forms  of  uric  acid 
crystals  than  those  mentioned,  and  practice  soon  teaches 
one  to  recognize  these  varied  forms,  even  though  they  may 
deviate  much  from  the  typical  shape.  The  rosette  form 
(Plate  5)  may  at  times  be  fan  shaped  ;  and,  again,  the  indi- 
vidual crystals  may  have  coalesced  so  as  to  form  a  large, 
solid,  compact  spherule,  often  with  sharp  spicules  projecting. 
These  large  rosettes  and  spherules  of  uric  acid  frequently 
have  the  appearance  of  particles  of  sand,  hence  the  term 
uric  acid  sand.     Occasionally,  the  coalescence  of  the  uric 


Fig.  26. — Forms  of  uric  acid  :  i,  Rhombic  plates ;  2,  whetstone  forms  ;  3, 3,  quadrate 
forms ;  4,  5,  prolonged  into  points  ;  6,  8,  rosettes  ;  7,  pointed  bundles ;  9,  barrel  forms 
precipitated  by  adding  hydrochloric  acid  to  urine. 


acid  cr>^stals  results  in  much  larger  bodies,  which  have  been 
termed  wic  acid  gravel,  and  still  larger,  uric  acid  calculi. 
Ultzmann  claims  that  the  irregular  forms  of  uric  acid,  espe- 
cially the  rough  and  pointed  forms,  are  almost  always  an 
accompaniment  of  uric  acid  calculi. 

Uric  acid  crystals  may  be  either  primary  (those  separating 
from  the  urine  inside  the  body)  or  secondary  (those  separating 
from  the  urine  outside  the  body),  but  the  author  knows  of 
no  certain  means  from  the  appearance  of  the  crystals  them- 
selves of  distinguishing  between  the  two.  The  only  certain 
14 


210  URINARY   SEDIMENTS. 

means  of  determining  the  presence  of  the  primary  crystals 
is  to  obtain  a  freshly  passed  specimen  and,  after  thoroughly 
agitating,  centrifugalize  while  still  warm — it  may  be  neces- 
sary to  centrifugalize  several  portions  in  order  to  obtain  the 
crystals,  if  present.  With  these  precautions,  any  crystals 
found  are  primary  ;  such  crystals  are  usually  highly  col- 
ored, compact,  and  in  the  form  of  the  rosette  or  spiculated 
spherule,  although  other  forms  may  be  primary. 

All  acid  urines  tend  to  deposit  their  uric  acid  sooner  or 
later.  The  time  of  on. set  of  precipitation  varies  from  a 
few  hours  to  five  or  six  days,  or  even  longer.  It  possesses 
a  strong  tendency  to  crystallize  upon  contact  with  any 
organic  or  inorganic  substances  ;  thus,  upon  standing  the 
crystals  often  cling  to  the  sides  of  the  glass  or  to  threads 
or  specks  suspended  in  the  urine.  This  fact  renders  it 
more  liable  than  any  other  crystalline  deposit  to  form  about 


/ 


Fig.  27. — Acid  sodium  urate  crystals. 

a  nucleus  in  the  urinary  tract  and  result  in  gravel  or  cal- 
culi. 

Urates. — (a)  Acid  Sodium  Urate. — This  salt  of  uric 
acid  occurs  in  urine  of  acid,  neutral,  or  faintly  alkaline  reac- 
tion, and  is  generally  amorphous,  but  sometimes  crystalline. 
When  amorphous,  it  forms  a  predominant  part  of  the  de- 
posit of  amorphous  or  mixed  urates,  seen  in  the  bottom  of  the 
vessel  after  the  urine  cools.  It  crystallizes  in  colorless, 
prismatic,  needle-like  crystals,  which  are  usually  arranged  in 
stellate  (star-like)  clusters.  (Fig.  27.)  Occasionally,  the 
needle  crystals  are  found  alone.  Sometimes  the  clusters 
have  a  dumb-bell  appearance,  each  half  of  which  is  striated 
and  broad  at  the  extremities  ;  one-half  of  one  of  the 
dumb-bell-like  clusters,  viewed  from  above,  would  be  fan 
shaped. 

Acid  sodium  urate  is  very  insoluble  in  cold  water  (1200 
parts)  but  quite  soluble  in  hot  water. 


Plate  5 


Uric- ACID  Crystals  with  Amorphous  Urates  (after  Peyer). 


URIC   ACID   AND   URATES. 


211 


(b)  Acid  Ammonium  Urate. — This  is  crystalline  and 
occurs  in  the  urinary  sediment  as  yellowish-red  or  dark- 
brown  spherules,  which  are  studded  with  fine,  sharp-pointed 
spicules.  To  these  the  terms  "  thorn-apple  crystals  "  and 
"hedge-hog  crystals"  have  been  given.  These  spicules 
may  be  short  or  long,  sometimes  branched,  curved,  or 
bent.  (See  Plate  6.)  It  also  frequently  crystallizes  in 
fine  needles,  which  are  in  clumps,  having  a  sheaf-of-wheat 
arrangement ;  and  sometimes  in  the  center  of  a  clump  a 
small  spherule  may  be  found  embedded.  These  crystals 
are  also  colored  dark-brown,  and  should  not  be  mistaken 
for  tyrosin   crystals  or  the  groups  of  colorless  crystals  of 


Fig.  28.— Deposits  in  amnioniacal  urine  (alkaline  fermentation)  :  A,  Acid  amnnmium 
urate;  B.  ammonio-magnesium  phosphate ;  C,  bacterium  ureae. 


acid  sodium  urate,  although  by  some  they  are  considered 
identical  with  the  latter. 

The  crystals  of  acid  ammonium  urate  are  soluble  in  iiot 
water,  and  dissolve  in  hydrochloric  acid  and  other  acids, 
with  the  subsequent  precipitation  of  uric  acid  crystals. 
When  they  are  treated  with  potassic  hydrate,  the  odor  of 
ammonium  is  evolved. 

The  crystals  often  occur  in  acid  urine  with  a  deposit  of 
amorphous  urates.  They  are  very  frequently  deposited 
during  the  alkaline  fermentation  of  the  urine,  and  are  found, 
along  with  amorphous  earthy  pho.sphates  and  crystals  of 
ammonio-magnesium  phosphate.  (Fig.  28.)  It  is,  in  fact, 
the  only  urate  found  in  strongly  alkaline  urine. 


212  URINARY   SEDIMENTS. 

(c)  Acid  Potassium  Urate. — This  exists  in  acid  urine, 
is  amorphous,  and  forms  a  part  of  a  deposit  of  amorphous 
urates.  Like  acid  sodium  urate,  it  is  very  insoluble  in  cold 
and  quite  soluble  in  hot  water. 

(d)  Acid  calcium  urate  is  a  constituent  of  acid  urine, 
but  occurs  only  rarely  and  usually  in  small  quantity  in  a 
deposit  of  amorphous  urates.  It  is  an  amorphous  white 
powder,  difficultly  soluble  in  cold  water,  faintly  soluble  in 
hot  water,  and  is  known  to  have  calcium  for  its  base,  since, 
upon  incineration,  it  leaves  a  residue  of  calcium   carbonate. 

Amorphous  or  Mixed  Urates. — These  consist,  as 
mentioned,  of  acid  sodium  urate,  acid  potassium  urate, 
ammonium  urate,  and  sometimes  acid  calcium  and  mag- 
nesium urates.  A  deposit  of  amorphous  urates  frequently 
occurs  in  urine,  more  especially  in  concentrated  urine, 
upon  cooling  to  the  room-temperature,  and  particularly  if 
subjected  to  a  low  temperature.  The  deposit  usually 
falls  rapidly  to  the  bottom  of  the  urine  glass,  and  when 
settled,  has  a  pink  or  yellowish-red  color  due  to  uroery- 
thrin  ;  it  may  rarely  be  colorless.  Occasionally,  a  portion 
of  the  deposit  is  so  finely  divided  that  it  will  not  settle,  the 
urine  remaining  turbid  throughout ;  but  even  under  such 
circumstances  the  greater  part  settles,  forming  a  heavy 
deposit. 

Detection  of  Amorphous  Urates. — First  determine  the 
reaction  of  the  urine,  and  if  acid,  pour  a  small  portion  of 
the  turbid  urine  into  a  test-tube  and  heat  gently,  but  avoid 
the  boiling  temperature.  If  amorphous  urates  are  present, 
they  are  dissolved  by  the  heat,  and  the  urine  becomes  clear. 
They  are  dissolved  by  an  alkaline  hydrate,  but  with  the 
simultaneous  precipitation  of  the  earthy  pho.sphates.  When 
amorphous  urates  are  treated  with  acetic  acid  or  any  of  the 
strong  mineral  acids,  they  are  dissolved,  with  the  subse- 
quent crystallization  of  uric  acid.  They  also  respond  to 
the  murexide  test. 

Treatment  of  a  Sediment  Containing  Amorphous 
Urates. — It  is  obvious  that  when  a  sediment  consists  chiefly 
of  amorphous  urates,  most  of  the  formed  elements  will  be 
obscured  by  the  abundance  of  urate  granules  ;  it,  therefore, 
becomes  necessary  to  get  rid  of  the  amorphous  urates  be- 
fore a  satisfactory  microscopic  examination  can  be  made. 
This  is  best  accomplished  in  the  following  manner  : 

Fill  a  urine  glass  with  the   urine,  allow  the  sediment  to 


Plate  6 


Ammonium  Urate,  showing  Spherules  and  Thorn-apple-shaped 
Crystals  (after  Peyer). 


URIC   ACID   AND    URATES.  213 

settle  thoroughly  ;  decant  the  supernatant  urine,  and  then 
add  warm  water  to  the  sediment,  using  an  amount  of  water 
equal  to  the  quantity  of  urine  originally  taken.  The  warm 
water  dissolves  the  urates  and,  at  the  same  time,  dilutes  the 
urine  so  that  they  will  not  reform.  Then  allow  the  sedi- 
ment to  settle  again,  or  centrifugalize,  and  examine  in  the 
usual  way. 

Aside  from  the  solution  of  the  urates,  the  addition  of 
warm  water  modifies  the  sediment  in  only  one  particular — 
/.  e.,  any  normal  blood  present  will  become  swollen  and  lose 
its  color  (abnormal  blood). 

Care  should  be  taken  to  avoid  the  use  of  boiling  water, 
or  water  having  a  high  temperature,  else  any  albumin 
present  will  be  coagulated,  rendering  the  sediment  unfit 
for  examination. 

Clinical  Significance. — /.  Uric  Acid :  Uric  acid  crys- 
tals are  frequently  found  in  the  urine  of  persons  who  are  in 
perfect  health,  especially  when  the  urine  is  concentrated  or 
unusually  acid.  As  has  been  mentioned,  a  deposit  of  uric 
acid  crystals  does  not  necessarily  indicate  an  increase  of  uric 
acid  in  the  urine,  for,  as  a  matter  of  fact,  a  deposit  may 
occur  even  when  the  uric  acid  is  much  diminished.  Any 
urine  upon  standing  for  several  hours  is  apt  to  deposit 
crystals  of  uric  acid.  Under  such  circumstances  crystals  of 
uric  acid  are  of  no  clinical  importance. 

A  deposit  of  uric  acid  is  often  the  result  of  a  hearty  meat 
diet,  especially  when  coupled  with  sedentary  habits  of  life 
and  faulty  digestion.  Likewise,  a  deposit  is  frequently  a 
result  of  increased  tissue  metabolism  and,  consequently,  an 
increased  formation  of  uric  acid,  attended  with  emaciation, 
headaches,  and  nervous  debility.  An  increased  formation 
of  uric  acid  is  sometimes  the  result  of  conditions  in  which 
the  oxidizing  power  of  the  system  is  seriously  impaired,  as 
in  diseases  of  the  respiratory  tract  and  circulatory  organs. 

Uric  acid  sediments  are  often  met  with  in  acute  febrile 
conditions,  in  which  there  is  a  marked  diminution  in  the 
aqueous  element  and  an  increased  acidity.  A  deposit  of 
uric  acid  is  of  frequent  occurrence  in  gout,  especially  fol- 
lowing a  paroxysm  ;  also  in  the  early  stages  of  chronic 
interstitial  nephritis,  particularly  when  the  disease  is  the 
result  of  gout.  Given,  then,  a  patient  with  gouty  ten- 
dencies, who  has  habitually  taken  a  hearty  meat  diet,  and 
whose  urine  shows  a  constant  deposit  of  uric  acid  cr>'stals 


214  URINARY   SEDIMENTS. 

and  evidences  of  more  or  less  renal  disturbance,  an  early- 
stage  of  chronic  interstitial  nephritis  should  be  strongly 
suspected.  Crystals  of  uric  acid  are  frequently  seen  tem- 
porarily in  the  sediment  during  the  convalescent  stage  of 
an  acute  diffuse  nephritis. 

In  the  urine  of  children  who  are  convalescing  from  scarlet 
fever  or  other  acute  exanthem,  uric  acid  deposits  are  very 
apt  to  occur,  and  even  uric  acid  gravel  may  be  found  under 
such  circumstances. 

Primary  uric  acid,  or  that  formed  inside  the  body,  is 
always  of  importance.  It  is  frequently  accompanied  by 
evidences  of  marked  irritation  of  the  kidney  or  other  por- 
tion of  the  urinary  tract.  The  primary  crystals  should  in 
all  instances  be  distinguished  from  those  that  are  secondarily 
formed.     (See  p.  209.) 

2.  Urates :  A  deposit  of  amorphous  urates,  like  uric  acid, 
often  occurs  in  any  urine  that  is  concentrated  or  unusually 
acid,  seen  especially  in  acute  febrile  diseases.  In  diseases 
of  the  liver  and  heart,  also  in  subacute  glomerular  (paren- 
chymatous) nephritis,  a  deposit  of  amorphous  urates  often 
takes  place.  A  primary  deposit  of  acid  ammonium  urate 
is  of  frequent  occurrence  in  the  kidneys  of  the  new-born, 
and  crystals  of  the  same  may  be  found  in  the  urine. 
Further  than  this,  the  clinical  importance  of  urates  is  much 
the  same  as  that  of  uric  acid.  It  should  be  borne  in  mind 
that  urines  that  are  allowed  to  stand  in  a  cold  place  are  very 
apt  to  deposit  amorphous  urates. 

Phosphates. — The  earthy  phosphates  are  the  only  salts 
of  phosphoric  acid  that  appear  in  the  urinary  sediment. 
They  consist  of  (^)  auunonio-niagnesijini  pJiospJiate  or  triple 
phosphate,  and  {b)  calcium  pJiosphate.  These  deposits  are 
found  only  in  very  feebly  acid,  neutral,  or  alkaline  urine,  and 
are  most  abundant  following  the  alkaline  fermentation. 
They  appear  to  the  naked  eye  as  bulky,  opaque,  white  de- 
posits, unless  they  are  accompanied  by  blood,  with  which 
they  are  then  more  or  less  tinged.  The  urine  itself  is  likely 
to  be  turbid  from  the  presence  of  amorphous  phosphate  of 
calcium  in  suspension,  especially  after  a  vegetable  diet.  It 
often  has  an  ammoniacal  and  sometimes  a  fetid  odor,  though 
not  necessarily.  Phosphatic  deposits  are  especially  abun- 
dant in  the  urine  of  some  affections  of  the  bladder,  and  often 
attend  diseases  of  the  spinal  cord,  because  of  paralysis  of 
the  bladder  and  consequent  retention  of  urine. 


PHOSPHATES. 


215 


(a)  Ammonio-magnesium  phosphate,  MgNH^PO^.- 
6H./J,  or  triple  phosphate,  is  a  crystalline  deposit  occurring 
in  two  forms  : 

1.  The  triangular  prism  with  beveled  edges  is  most 
typical  and  frequent.  (Fig.  29.)  There  are  many  modifi- 
cations of  this  type,  one  of  the  most  common  being  the  so- 
called  "  cofifin-lid  "  crystal,  which  is  the  triangular  prism  with 
one  of  the  three  angles  wanting.  Frequently,  the  crystals 
are  shortened  so  as  to  form  squares,  and  these  are  the  ones 
already  referred  to  as  being  possibly  mistaken  for  the  octa- 
hedral crystals  of  calcium  oxalate. 

2.  The  stellate  or  feathery  crystals  of  triple  phosphate 
(Fig.  29)  are  less  commonly  seen.      They  predominate  in 


Fig.  29. — Triple-phosphate  crystals. 

the  precipitate  that  follows  the  addition  to  the  urine  of 
ammonic  hydrate.  These  crystals  gradually  undergo  con- 
version into  the  prismatic  form. 

(b)  Calcium  phosphate  is  either  amorphous  (normal 
salt,  Ca^{VO^).^  or  crystalline  (acid  salt,  CaHPOJ.  (i) 
The  aniorpJunis  form  is  most  frequently  found  as  a  whitish 
flocculent  deposit  ^  in  the  after-meal  urine.  It  is  often 
precipitated  from  the  urine  by  heat,  and  constitutes  an 
important  source  of  error  in  testing  for  albumin  by  heat ; 
this  precipitate  is  readily  dissolved  by  acetic  acid.  This 
form  of  calcium  phosphate  sometimes  occurs  in  a  very 
feebly  acid  urine  as  minute,  pale,  highly  refractive  granules. 


^  This  deposit  usually  consists  partly  of  magnesium  phosphate. 


216  URINARY   SEDIMENTS. 

which  are  arranged  in  irregular  clumps,  and  often  adherent 
to  renal  casts  or  other  organized  elements  of  the  sediment. 
Amorphous  phosphate  of  lime  is  a  frequent  accompaniment 
of  triple  phosphate  in  a  neutral  or  alkaline  urine. 

(.?)  Acid  calcium  pJwsphate,  or  the  crystalline  form,  is  fre- 
quently found  in  urinary  deposits,  and  is  often  mistaken  for 
the  crystals  of  acid  urate  of  sodium.  Crystals  of  acid 
phosphate  of  calcium  sometimes  occur  alone,  sometimes  with 
crystals  of  triple  phosphate,  and  not  infrequently  with  the 
amorphous  form  of  calcium  phosphate.  They  are  also  met 
with  in  a  urine  of  weak  acid  reaction,  but  one  that  is  about 
to  undergo  the  alkaline  fermentation.  Acid  calcium  phos- 
phate crystallizes  in  the  form  of  prisms  that  are  found  either 
singly  or  in  stellate  groups.  (Fig.  30.)  Frequently,  the 
groups  have  a  fan-like,  and  sometimes  a  club-like,  arrange- 


Fig.  30.— Acid  calcium  phosphate  crystals. 

ment.  Usually,  the  individual  crystals  are  small,  but  may 
be  large  and  thick,  with  one  end  beveled  to  a  sharp  point, 
with  cutting-edges  on  each  side. 

It  is  often  impossible  to  decide  from  the  microscopic 
appearance  of  these  crystals  whether  they  are  acid  calcium 
phosphate  or  acid  sodium  urate,  especially  when  found  in 
a  faintly  acid  urine.  These  two  forms  of  crystals  are  dis- 
tinguished by  treating  them  with  acetic  acid,  which  rapidly 
dissolves  the  phosphate  crystal,  while  that  of  acid  sodium 
urate  is  more  slowly  dissolved,  and  is  subsequently  replaced 
by  crystals  of  uric  acid.  The  crystals  of  acid  calcium  phos- 
phate are  often  accompanied  by  crystals  of  calcium  oxalate. 

Clinical  Significance. — It  has  already  been  shown  (p. 
29)  that  a  deposit  of  amorphous  phosphates  may  occur  in 
health  in  a  urine  alkaline  from  fixed  alkalies,  notably  two 
or  three  hours  after  a  hearty  meal.      If  this  deposit  be  tem- 


CALCIUM   OXALATE.  217 

porary,  it  is  of  no  clinical  importance  ;  if,  however,  it  be 
permanent,  and  the  twenty-four-hour  urine  contain  a  heavy 
deposit  of  amorphous  phosphates,  it  becomes  of  pathologic 
importance,  and  in  most  instances  indicates  a  low  general 
metabolism.  Ordinary  tonic  treatment  usually  results  in  a 
complete  disappearance  of  the  deposit. 

Crystalline  phosphates  when  deposited  zvithiii  tlic  body, 
often  cause  much  damage  to  the  urinary  tract.  Such  de- 
posits consist  chiefly  of  crystals  of  ammonio-magnesium 
phosphate  formed  as  the  result  of  the  presence  of  a  vola- 
tile alkali — ammonia  which  arises  from  the  decomposition 
of  the  urea  in  the  urinary  passages.  This  is  most  com- 
monly encountered  in  cases  of  chronic  cystitis,  chronic  pye- 
litis, and  pyelocystitis,  in  which  the  clinical  symptoms  are 
mostly  irritant  in  character.  The  mechanical  irritation  by  the 
crystals, ////.y  the  irritating  effect  of  the  ammonia,  adds  much 
to  the  distress  of  the  patient.  The  most  frequent  causes  of 
this  condition  of  the  urine  are  obstructive  diseases  of  the 
lower  urinary  tract.  Likewise,  those  diseases  that  affect 
the  contractile  power  of  the  muscles  of  the  bladder.  Thus, 
in  enlarged  prostate,  diseases  of  the  spinal  cord,  paraplegia, 
etc.,  the  urine  is  retained,  and  soon  undergoes  ammoniacal 
fermentation  with  a  resulting  deposit  of  triple  phosphate. 
This  condition  of  the  urine  nearly  always  precedes  the  so- 
called  "  surgical  kidney  "  and  other  dangerous  septic  con- 
ditions that  also  often  result  from  the  introduction  of  un- 
clean instruments  into  the  bladder. 

Calcium  Oxalate.^ — Crystals  of  oxalate  of  calcium  are 
found  in  either  acid  or  alkaline  urine,  but  most  commonly 
in  acid  urine  ;  they  are  frequently  associated  with  crystals  of 
uric  acid.  When  present  in  an  alkaline  urine,  they  are 
usually  found  along  with  crystals  of  ammonio-magnesium 
phosphate,  for  which  they  are  frequently  mistaken. 

When  crystals  of  calcium  oxalate  are  constantly  present 
in  the  urine,  the  condition  is  termed  oxahtria. 

Calcium  oxalate  crystallizes  in  two  typical  forms — the 
octalicdral  and  dumb-bell  crystals.  There  are,  however, 
various  modifications  of  these  two  forms,  according  to  the 
positions  of  the  crystals.      (Fig.  31.) 

I.  The  octahedral  crystals  are  made  up  of  two  four- 
sided  pyramids,  placed  base  to  base,  and  when  viewed  from 

1  For  the  properties  of  Calcium  Oxalate  see  p.  96. 


218  URINARY    SEDIMENTS. 

the  side,  their  characteristic  appearance  is  that  of  a  square 
crossed  obhquely  by  two  bright  lines,  forming  the  so-called 
"  envelop  "  crystal.  If,  however,  the  octahedron  be  turned 
with  one  of  its  long  axes  toward  the  observer  while  the 
other  is  held  upright,  the  short  axis  will  necessarily  be 
transverse,  and  the  crystal  will  appear  as  a  long  and  very 
acute  octahedron. 

Frequently,  the  octahedra  coalesce  in  such  a  way  as  to 
have  the  appearance  of  an  open  umbrella,  constituting  the 
so-called  "umbrella"  crystals.  Sometimes  each  half  of 
an  octahedron  is  connected  by  a  short  quadrilateral  prism, 
and  such  have  been  called  "  prismatic  "  crystals  of  calcium 
oxalate.  A  kw  other  irregular  forms  are  occasionally 
found,  but  most  of  them,  if  not  all,  are  modifications  of  the 
typical  octahedron.      Occasionally,  a  number  of  the  octa- 


o    ry  "  ^ 


Fig.  31. — Various  forms  of  calcium  oxalate  crj'stals. 

hedral  crystals  are  found  intimately  adherent,  forming 
larger  or  smaller  microscopic  concretions.  Isolated  crystals 
are  not  infrequently  found  adherent  to  renal  casts. 

2.  The  dumb-bell  and  oval  crystals  of  calcium  oxalate 
are  more  rarely  found  in  the  urinary  sediment  than  the 
octahedral  forms,  but  when  thus  met  with,  are  highly  char- 
acteristic. The  dumb-bell  crystals  are  always  associated 
with  a  larger  or  smaller  number  of  oval  or  circular  forms, 
which  have  bright  centers  showing  their  biconcavity.  In 
addition  to  these  are  found  allied  forms,  especially  those 
with  partial  concavities  at  the  sides.  Frequently,  two  dumb- 
bells are  found  crossed  at  their  centers,  forming  a  double 
dumb-bell  crystal.  These  colorless  dumb-bell  crystals  of 
calcium  oxalate  should  not  be  mistaken  for  the  yellowish-red 


CALCIUM    OXALATE.  219 

or  brown  dumb-bells  of  uric  acid  and  of  ammonium  urate. 
The  dumb-bells  of  uric  acid  and  of  ammonium  urate  are 
readily  soluble  in  alkaline  hydrates,  while  those  of  calcium 
oxalate  are  difficultly  soluble  ;  the  dumb-bells  of  uric  acid 
are  insoluble  in  dilute  hydrochloric  acid,  while  those  of 
calcium  oxalate  are  soluble.  The  dumb-bell  or  oval  crys- 
tals of  calcium  oxalate  are,  like  the  octahedral  forms,  quite 
often  found  adherent  to  renal  casts,  and  a  number  of  them 
may  be  joined  together  to  form  microscopic  concretions. 

The  small  circular  ciystals  are  sometimes  mistaken  for 
normal  blood  globules.  They  are  readily  distinguished  by 
the  fact  that  the  oxalate,  although  biconcave,  is  very  highly 
refractive,  colorless,  and  insoluble  in  acetic  acid,  whereas 
the  normal  blood  globule  has  a  pale-yellow  color,  and  is 
rendered  abnormal  by  acetic  acid. 

Primary  and  Secondary  Crystals  of  Calcium  Oxalate. 
— The  primary  crystals,  or  those  formed  inside  the  body, 
are  generally  the  large  octahcdra,  and  also  most  of  the  oval 
2ir\d  dumb-bell  forms.  Secondary  crystals,  or  those  formed 
after  the  urine  has  been  passed,  are  usually  the  small 
oetahedra  and  perhaps  some  of  the  very  small  oval,  circular, 
and  dumb-bell  forms.  These  secondary  crystals  are  most 
commonly  found  in  a  urine  that  has  been  allowed  to  stand 
for  some  time,  when  they  are  frequently  accompanied  by 
uric  acid.  Only  rarely  are  the  large  crystals  deposited 
secondarily  ;  they  may,  however,  be  deposited  following  the 
addition  of  acetic  acid  to  the  urine. 

Distinction  Betiveen  Crystals  of  Calcium  Oxalate  and 
Those  of  Ammonio-magnesium  Phosphate. — The  fact  that,  at 
times,  some  of  the  crystals  of  ammonio-magnesium  phos- 
phate (triple  phosphate)  closely  resemble  the  octahedral 
form  of  calcium  oxalate  often  leads  to  much  confusion. 
These  are  the  small  crystals  of  triple  phosphate,  modifica- 
tions of  the  typical  triangular  prism,  with  its  beveled  ends, 
in  which  the  body  of  the  prism,  instead  of  being  a  parallelo- 
gram, is  nearly  square,  and  in  which  the  line  connecting  the 
beveled  ends  is  exceedingly  short,  but  rarely  so  short  as 
not  to  be  seen  by  careful  focusing.  The  nature  of  the  crys- 
tals may,  however,  be  determined  by  the  characteristic 
shape  of  the  larger  crystals  about  them,  for  they  never 
occur  alone.  As  previously  mentioned,  the  octahedron  of 
calcium  oxalate  is  usually  a  square  crossed  by  two  diagonal 
lines,  and  therefore  has  the  appearance  of  an  envelop.    The 


220  URINARY  SEDIMENTS. 

phosphate  crystals  are  promptly  dissolved  by  acetic  acid, 
while  those  of  the  oxalate  of  lime  are  insoluble  in  this  acid. 

Clinical  Significance. — Crystals  of  calcium  oxalate  may 
be  found  in  the  urine  of  persons  who  are  typically  healthy, 
as  well  as  in  certain  diseased  conditions.  In  licalth  the 
presence  of  an  oxaluria  is  dependent  upon  the  character  of 
the  food  ingested.  Thus,  it  often  follows  the  ingestion  of 
rhubarb,  onions,  sorrel,  tomatoes,  grapes,  and  the  like, 
because  of  the  amount  of  oxalic  acid  contained  in  these 
substances.  It  is  of  frequent  occurrence  in  various  dis- 
turbances of  digestion.  It  often  follows  the  abundant 
ingestion  of  carbohydrates,  and  the  use  of  an  excessive 
meat  diet ;  this  is  especially  the  case  when  there  is  any 
interference  with  the  oxidizing  power  of  the  system.  We 
know  that  oxalic  acid  is  formed  as  an  intermediate  product 
of  the  metabolism  between  uric  acid  and  urea  ;  that  the 
process  of  formation  appears  to  be  one  of  oxidation  which, 
if  diminished,  results  in  an  oxaluria.  Thus,  in  diseases  of  the 
heart  a7id  lungs  an  oxaluria  is  of  frequent  occurrence.  It 
is  commonly  seen  in  diseases  of  the  nervous  system,  and  it 
is  claimed  by  some  that  the  oxalic  acid  present  in  the 
blood,  on  account  of  its  poisonous  action,  causes  a  certain 
train  of  symptoms  of  which  nervous  phenomena  are  espe- 
cially prominent.  This  constitutes  the  theory  of  so-called 
''  oxalic-acid  diathesis."  It  is  true  that  oxalic  acid,  when 
taken  internally  in  considerable  amount,  exerts  a  poisonous 
action  upon  the  organism,  not  only  locally  on  the  digestive 
tract,  but  upon  the  heart  and  nervous  system.  However, 
further  evidence  is  necessary  to  prove  that  the  symptoms 
of  the  so-called  "  oxalic-acid  diathesis  "  are  directly  due  to 
an  increased  formation  of  oxalic  acid,  or  its  retention  in  the 
blood. 

The  primary  crystals  of  calcium  oxalate  often  set  up  a 
more  or  less  marked  irritation  of  the  urinary  tract,  espe- 
cially if  they  separate  from  the  urine  in  the  kidney  or  renal 
pelvis  ;  the  mechanical  action  is  usually  much  less  severe 
if  the  crystals  separate  in  the  bladder.  The  irritation 
thereby  may  be  very  severe  and  even  be  accompanied  by 
abundant  hemorrhage.  Such  a  severe  mechanical  disturb- 
ance is  invariably  accompanied  by  pain,  often  frequent  and 
painful  micturition,  and  usually  by  a  more  or  less  concen- 
trated urine.  If  the  separation  of  these  primary  crystals  con- 
tinues for  some  time,  the  tendency  to  a  calculus-formation 


CYSTIN.  221 

in  the  pelvis  of  the  kidney  or  bladder  is  very  great,  and 
especially  in  those  cases  in  which  there  is  more  oi  less 
hemorrhage. 

In  the  more  severe  forms  of  oxaluria  the  condition  has 
been  incorrectly  termed  "  false  Bright's  disease,"  owing  to 
the  extreme  nervous  symptoms,  emaciation,  dry  skin,  con- 
stant pain  or  a  sense  of  weight  across  the  loins,  frequency 
of  micturition,  and  other  symptoms  similar  to  those  that 
accompany  a  nephritis. 

Cystin.' — Cystin,  (CjHgNSO,),,  is  an  amido-acid,  and  con- 
stitutes one  of  the  rarer  forms  of  abnormal  urinary  sedi- 
ments. It  crystallizes  in  the  form  of  colorless  hexagonal 
plates  (Fig.  32),  the  angles  of  which  measure  120  degrees. 
The  sides  of  these  plates  are  usually  equal,  although  rarely 
two  sides  are  found  to  be  longer  or  shorter  than  the  other 


O 


O 


O 


<2) 

Fig.  32. — Cystin  cn-stals. 


four.  It  also  crystallizes  in  quadrilateral  prisms  or  groups 
of  prisms.  Crystals  of  cystin  have  an  opalescent  luster, 
and  are  often  arranged  in  rosettes. 

Cystin  is  insoluble  in  water,  alcohol,  and  ether;  also  in 
-acetic  and  tartaric  acids.  It  is  soluble  in  mineral  acids  and 
oxalic  acid,  in  amnionic  hydrate  and  other  alkaline  hydrates 
and  carbonates,  but  is  insoluble  in  ammonic  carbonate.  It 
is  readily  precipitated  from,  its  alkaline  solution  by  acetic 
acid.  Its  solutions  rotate  the  plane  of  polarized  light 
strongly  toward  the  left. 

Cystin  contains  26  per  cent,  sulphur,  the  odor  of  sul- 
phureted  hydrogen  being  evolved  when  a  urine  containing 
cystin  undergoes  ammoniacal  fermentation. 

Cystin  is  probably  not  a  normal  constituent  of  the  urine, 
although  Goldmann  and  Baumann  claim  to  have  isolated 
a   substance  resembling  cystin,  in  very  small  quantities  as 


222  URINARY  SEDIMENTS. 

a  benzoyl  compound  from  normal  urine.  Under  pathologic 
conditions  the  quantity  of  cystin  in  the  urine  undergoes 
considerable  variation  at  different  times,  and  it  may  tem- 
porarily disappear.  The  daily  quantity  may  reach  as  high 
as  1.5  grams  (Toel) ;  ordinarily,  however,  it  varies  between 
a  few  milligrams  and  one  gram. 

Cause  of  Cystimiria. — Until  recently  the  cause  of  cystin - 
uria  was  thought  to  be  due  to  abnormal  processes  of  oxida- 
tion in  the  liver,  since,  in  some  respects,  cystin  resembled 
taiirin.  Marowski  ^  considered  it  a  vicarious  elimination 
of  taurin  because  in  his  case  there  was  an  absence  of  bile 
in  the  intestine. 

The  experiments  of  Baumann  and  v.  Udranszky,  Brieger, 
and  others,  threw  new  light  on  the  causation  of  this  condi- 
tion. They  found  that  certain  products  of  intestinal  putre- 
faction, called  diamines,  were  eliminated  in  the  urine  and 
feces  of  persons  afflicted  with  cystin  uria.  Baumann  and 
V.  Udranszky  ^  made  frequent  examinations  of  the  urine  of 
a  case  of  cystinuria  for  diamines,  and  found  them  regularly. 
They  were  isolated  in  the  form  of  a  benzoyl  compound, 
which  varied  in  amount  from  0.2  to  0.4  gram  in  twenty- 
four  hours.  Approximately,  one-third  to  one-fourth  of 
these  substances  existed  as  tetramethylendiamine,  and  the 
remainder  as  pentamethylendiamine.  ^  According  to  Brie- 
ger, since  these  diamines  arise  only  as  a  result  of  putre- 
factive processes  due  to  specific  bacteria,  cystinuria  can  be 
considered  the  result  of  a  specific  infection  of  the  intestine. 
In  Baumann's  case  both  diamines  were  invariably  found  in 
the  feces  as  well  as  in  the  urine,  and  he  observed  that  the 
relative  amounts  of  these  substances  in  the  feces,  especially 
the  cadaverin,  varied  inversely  as  those  in  the  urine. 
Neither  Brieger  nor  Baumann  was  able  to  discover  these 
diamines  in  the  feces  of  healthy  individuals,  or  in  those 
suffering  from  other  diseases.* 

So  far  as  has  yet  been  determined,  no  definite  relation 
exists   between   the  formation   of  cystin  and  the  diamines, 

'  "  Deutsches  Archiv  f.  klin.  Med.,"  iv,  S.  449. 

2  "Zeitschr.  f.  physiol.   Chem.,"  1889,  xiil,  S.  562. 

•'  Brieger  gave  new  names  to  these  two  substances,  calling  the  first  "  pu- 
trescin,"  and  the  latter  "cadaverin." 

*  According  to  Neubauer  and  Vogel,  these  diamines  have  been  found  in  the 
intestinal  discharges  of  patients  with  Asiatic  cholera. 


CYSTIN.  223 

although    the    same    conditions    that     produce    diaminuria 
usually  also  produce  cystinuria. 

Clinical  Significance. — Hereditary  predisposition  certainly 
appears  to  have  some  bearing  as  a  cause,  since  so  many 
cases  have  been  reported  of  the  existence  of  the  affection 
in  several  members  of  the  same  family.  It  is  difficult, 
however,  to  explain  the  hereditary  transmission  of  cystin- 
uria by  the  theory  of  Brieger,  unless  we  assume  that  such 
individuals  are  more  susceptible  to  the  action  of  the  "  spe- 
cific bacteria"  that  produce  the  intestinal  putrefaction  than 
others. 

Cystin  is  met  with  in  the  urine  of  both  infants  and  adults, 
but  only  rarely  occurs  in  old  age.  It  does  not  appear  to 
be  connected  with  any  local  or  constitutional  disease.  It 
may  be  present  and  continue  for  years  without  any  notice- 
able impairment  of  health,  although,  as  a  result  of  its  sepa- 
ration from  the  urine,  there  is  usually  more  or  less  irritation 
of  the  urinary  tract.  It  has  been  occasionally  observed  in 
cases  of  liver  disease,  and  Ebstein  has  noted  the  presence 
of  cystin  in  the  urine  of  cases  of  acute  articular  rheumatism. 
The  danger  of  a  calculus-formation  always  attends  the 
separation  of  cystin  from  the  urine  inside  the  body.  Where 
a  concretion  exists,  it  is  usual  to  find  few  (sometimes  many) 
isolated  crystals  of  cystin. 

Detection. — The  detection  of  cystin  is  based  chiefly  on  the 
recognition  of  the  characteristic  crystals  in  the  urinary 
sediment ;  also  their  solubility  in  weak  ammonic  hydrate, 
and  their  recrystallization  upon  the  evaporation  of  the 
ammonic  hydrate. 

It  is  always  important  to  distinguish  between  the  crystals 
of  cystin  and  other  like  crystalline  elements.  Cystin  can  be 
differentiated  from  the  pale,  six-sided  cr>'stals  of  uric  acid 
by  allowing  a  drop  of  weak  ammonic  hydrate  to  mingle 
with  the  deposit  on  a  glass  slide,  when  either  form  of  crys- 
tal will  disappear  ;  evaporate,  and  if  cystin  be  present,  the 
crystals  reappear  ;  if  uric  acid  be  present,  crystals  of  ammo- 
nium urate  will  be  found,  instead  of  those  of  uric  acid. 
Another  simple  method  consists  in  treating  the  crystals 
with  hydrochloric  acid,  which  readily  dissolves  the  cystin, 
but  leaves  uric  acid  unchanged.  Cystin  is  distinguished 
from  triple  phosphate  by  its  behavior  with  acetic  acid,  which 
quickly  dissolves  the  phosphate  crystals  while  those  of  cys- 
tin remain  unchanged. 


224  URINARY  SEDIMENTS. 

The  evolution  of  sulphurctcd  hydrogen  from  the  urine 
should  always  lead  to  an  examination  for  cystin,  although 
HjS  is  by  no  means  ahvays  due  to  the  presence  of  cystin. 
Frequently,  silver  coins  carried  in  the  pockets  of  persons 
suffering  from  cystinuria  are  blackened  by  the  sulphureted 
hydrogen  evolved,  owing  to  the  fact  that  cystin  is  some- 
times eliminated  by  the  skin,  where  it  decomposes  and  fur- 
nishes H2S.  ^ 

Bilirubin  and  Hematoidin. — Bilindnu  is  frequently  de- 
posited in  a  urine  containing  bile  in  an  amorphous  or  crys- 
talline form.  The  crystals  of  bilirubin  (Plate  7)  have  two 
forms — (i)  clusters  of  needles  arranged  as  stellates,  occur- 
ring either  free  in  the  urinary  sediment  or  found  attached  to 
cells  ;  and  (2)  minute  rhombic  tablets  or  plates  which  vary 
in  color  from  a  yellow  to  a  beautiful  ruby  red. 

They  are  soluble  in  caustic  soda,  and  on  the  application 
of  a  drop  of  nitric  acid  a  green  rim  forms  about  them. 

Hematoidin,  a  derivative  of  hematin,  was  first  discoxered 
by  Virchow  in  extravasated  blood.  It  resembles  bilirubin 
as  closely  in  appearance  as  in  its  chemic  properties.  The 
crystalline  formation  of  the  two  is  identical.  (Plate  7.) 
According  to  Hoppe-Seyler,  \^  Jaksch,  and  others,  the}' 
are  in  all  respects  indistinguishable,  and  it  is,  therefore,  safe 
to  say  that  they  are  one  and  the  same  substance  occurring 
under  vaiying  conditions. 

As  previously  stated,  these  crystals  are  very  commonly 
found  in  urine  containing  bile  ;  it  is  not  uncommon  to  find 
them  in  the  urinary  sediment  following  an  extensive  hemor- 
rhage, or  the  evacuation  of  an  abscess,  or  pyonephrosis  in 
which  there  has  been  hemorrhage.  Leyden  found  these 
crystals  in  nephritis  gravidarium  ;  Foltanek  and  Rosenheim 
in  acute  yellow  atrophy ;  and  v.  Jaksch  in  phosphorus- 
poisoning,  cirrhosis  of  the  liver,  as  well  as  in  severe  jaun- 
dice of  the  most  distinct  types.  The  author  has  occasion- 
ally met  with  these  crystals  in  hemorrhage  from  the  pros- 
tatic region,  once  in  cancer  of  the  bladder,  and  once  follow- 
ing a  traumatic  hemorrhage  from  the  kidneys,  as  well  as 
in  jaundice  from  various  causes. 

Leucin. — Leucin,  C^.H^gNO.,, — amidocaproic  acid, — is 
one  of  the  products  of  decomposition  of  proteid  bodies  or 
of  their  derivatives,  and  is  formed  by  the  activity  of  certain 

^  For  the  quantitative  determination  of  cystin  see  Neubauer  and  V'ogel, 
"Analyse  des  Harns,"  Bd.  i,  1898,  S.  807. 


Plate  7 


^         m 


Hematoidin  (Bilirubin)  Crystals. 


LEUCIN.  225 

ferments,  especially  trypsin.  As  a  urinary  deposit  it  is  of 
very  rare  occurrence.  It  is  usually  accompanied  by  crys- 
tals of  tyrosin. 

Leucin  occurs  as  highly  refractive  spherical  crystals, 
which  are  usually  marked  with  radiating  and  concentric 
striae.  (Fig.  33.)  When  pure,  it  crystallizes  in  very  delicate, 
small  plates,  often  of  irregular  shapes  and  with  a  greasy 
feel,  and  are  usually  arranged  in  groups  or  found  lying  one 
upon  another.  When  very  impure,  they  appear  as  yel- 
lowish, highly  refractive  globules,  apparently  without  crys- 
talline structure.  In  this  form  they  may  be  mistaken  for 
oil-drops,  but  by  careful  study  it  will  be  found  that  they 
are  less  highly  refractive  than  oil-drops — i.  e.,  not  possess- 
ing quite  so  wide  a  dark  border. 

Leucin,  when  pure,  is  difficultly  soluble  in  cold,  but  more 


Fig-  33- — Leucin  crystals. 

readily  soluble  in  hot,  water;  it  is  only  sparingly  soluble  in 
alcohol  ;  readily  soluble  in  acids  and  alkaline  hydrates,  and 
insoluble  in  ether.  When  impure,  its  solubility  is  distinctly 
increased.  Leucin  sublimes  without  melting  when  heated 
to  170°  C.  ;  at  a  higher  temperature  it  is  decomposed  into 
carbonic  acid  and  amylamin.  It  combines  with  bases  and 
acids  to  form  salts.  It  can  be  obtained  artificially  by  decom- 
posing proteids  with  acids. 

Detection. — Leucin  may  be  recognized  by  the  character- 
istic microscopic  appearance  of  its  crystals.  Having  found 
crystals  resembling  leucin,  confirmatory  tests  should  always 
be  employed. 

I.  When  leucin  is  evaporated  on  a  platinum  foil  with 
nitric  acid,  a  colorless  residue  remains,  which,  if  treated 
15 


226  URINARY  SEDIMENTS. 

with  a  few  drops  of  sodic  hydrate  and  heated,  furnishes, 
according  to  the  purity  of  the  leucin,  a  watery,  or  more  or 
less  colored,  fluid.  If  this  fluid  be  concentrated,  there  re- 
mains an  oily  fluid  that  does  not  adhere  to  the  platinum, 
but  collects  in  drops  of  varying  size  (Scherer). 

2.  On  the  addition  of  a  trace  of  chinon  and  a  few  drops 
of  sodic  hydrate  to  a  cold  aqueous  solution  of  leucin  a 
marked  violet  color  appears.  Other  amido-acids,  as  well 
as  certain  proteid  bodies,  give  this  reaction  (Wurster). 

3.  Leucin  does  not  give  a  color  reaction  with  furfurol, 
but  tyrosin,  on  the  other  hand,  gives  a  decided  reaction 
with  an  aqueous  solution  of  this  substance. 

Since  leucin  nearly  always  accompanies  tyrosin,  its 
clinical  importance  will  be  considered  under  the  subject  of 
tyrosin. 

Tyrosin. — Tyrosin,  CgHj^NOg,  like  leucin,  is  one  of  the 
products  of  the  decomposition  of  proteid  substances.  It 
crystallizes  in  the  form  of  exceedingly  fine  needles,  which 
are  arranged  in  sheaf-like  collections,  often  crossing  each 
other,  and  intersecting  at  their  constricted  middle  portions. 
It  also  crystallizes  in  rosettes  with  the  needles  radiating  from 
their  centers  (Fig.  34),  especially  if  crystallized  from  an 
alkaline  solution. 

The  crystals  are  colorless,  but  when  arranged  in  masses, 
often  look  dark,  especially  near  the  central  portions,  because 
of  the  compact  arrangement  of  the  needles.  They  are 
tasteless  and  odorless,  very  sparingly  soluble  in  cold  water 
(i  :  2000  at  20°  C),  but  much  more  soluble  in  boiling 
water  (i  :  150).  They  are  almost  insoluble  in  strong  alco- 
hol (i  :  135,000),  quite  insoluble  in  ether,  and  readily  solu- 
ble in  acid,  alkalies,  and  solutions  of  the  alkaline  salts. 
Tyrosin  readily  combines  with  bases  and  acids  to  form  dis- 
tinct compounds.  (For  details  see  Neubauer  and  Vogel, 
"Analyse  des  Harns,"  Bd.  i,  1898,  S.  281.) 

Tyrosin  that  has  been  isolated  from  the  urine  or  other 
fluids  is  readily  recognized,  even  when  present  in  very  small 
amounts,  by  means  of  Hoffmann's  and  Piria's  tests. 

Hoffmann' s  Test. — When  a  solution  of  tyrosin  or  a  sus- 
pected deposit  that  has  been  boiled  with  an  excess  of  water 
Ls  heated  with  Millon's  reagent,  a  bright  crimson  or  pink 
color  is  produced.  If  much  tyrosin  be  present,  a  similarly 
colored  precipitate  forms,  while  the  supernatant  fluid  remains 
red,  or  sometimes  a  purple-red. 


TYROSIN. 


227 


Piria's  Test. — If  ty rosin  be  treated  on  a  watch-glass  with 
a  Httle  concentrated  sulpiiuric  acid,  and  heated  on  a  water- 
bath  for  from  five  to  ten  minutes,  there  results  a  compound 
— tyrosin-sulphuric  acid — which  has  a  pink  color.  This 
pink  solution  is  then  diluted  with  water,  warmed,  neutral- 
ized with  barium  carbonate,  and  filtered  while  hot.  The 
colorless  and  neutral  filtrate  is  then  treated  with  a  few  drops 
of  a  very  dilute  solution  of  perchloride  of  iron,  which  pro- 
duces a  violet  color.  An  excess  of  the  iron  salt  should  be 
avoided,  as  it  readily  destroys  the  color. 

According  to  v.  Udranszky,i  a  characteristic  reaction  is 
obtained  when  an  aqueous  solution  of  furfurol  is  added  to  a 
solution  of  tyrosin. 


Fig.  34.— Tyrosin  crystals. 


Furfurol  Reaction. — Dissolve  a  small  crystal  of  tyrosin 
in  I  c.c.  of  water,  add  one  drop  of  a  0.5  per  cent,  solution  of 
furfurol,  and  then  underlie  with  concentrated  sulphuric  acid  ; 
the  fluid  is  colored  rose-red.  The  mixture  should  not  have 
a  temperature  above  50°  C. 

The  foregoing  tests  for  tyrosin  can  not  be  applied  directly 
to  the  urine  with  satisfactory  results,  since  various  urinary 
constituents  either  give  the  same  reactions  or  obscure  the 
tests.  It  is,  therefore,  necessary  to  isolate  the  tyrosin,  which, 
according  to  Blendermann,^  can  be  accomplished  in  the  fol- 
lowing manner : 

Precipitate  the  urine  with  basic  acetate  of  lead,  filter,  and 

^  "Zeitschr.  f.  physiol.  Chem.,"  xii,  355,  1888. 
'^  "Zeitschr.  f.  physiol.  Chem.,"  vi,  260,  1882. 


228  URINARY  SEDIMENTS. 

remove  the  lead  from  the  filtrate  by  passing  sulphureted 
hydrogen  through  it.  Filter,  and  evaporate  this  filtrate  to 
a  very  small  volume,  and  allow  it  to  stand  several  hours  to 
crystallize.  Filter,  dissolve  the  crystals  in  boiling  water,  and 
apply  the  tests  as  directed. 

If  the  urinary  sediment  contains  crystals  that  resemble 
tyrosin,  their  presence  should  always  be  confirmed  as  fol- 
lows :  Filter  off  the  sediment,  wash  with  water,  dissolve 
while  still  on  the  filter  in  hot  ammonic  hydrate  to  which 
some  ammonium  carbonate  has  previously  been  added,  evap- 
orate the  filtrate  to  crystallization,  and  examine  microscop- 
ically. 

Care  should  be  taken  not  to  mistake  the  large  hedgehog 
and  sheaf-like  crystals  of  acid  urate  of  ammonium,  also 
the  sheaf-like  crystals  of  acid  sodium  urate,  for  the  rosettes 
and  sheaves  of  tyrosin. 

Clinical  Significance. — Leucin  and  tyrosin  are  constantly 
formed  as  products  of  the  digestion  of  proteids,  particularly 
by  the  action  of  trypsin,  and  usually,  if  not  always,  occur 
together.  The  presence  of  these  substances  in  the  urine  is 
of  very  rare  occurrence.  It  is  claimed  by  some  observers 
that  they  are  present  in  minute  traces  in  normal  urine. 
This,  however,  is  still  an  unsettled  question,  as  certain  reli- 
able observers  have  been  unable  to  confirm  such  claims. 

Leucin  and  tyrosin  have  been  found  in  the  urine  in  con- 
siderable amounts  in  acute  yellow  atrophy  of  the  liver  and 
in  acute  phosphorus-poisoning.  They  have  also  been  ob- 
served in  the  urine  in  cases  of  severe  typhus  fever,  severe 
smallpox,  and  diseases  of  the  intestines.  The  appearance 
of  these  two  substances  in  disease  is  invariably  accompanied 
by  a  very  marked  reduction  in  the  quantity  of  urea. 

Cholesterin. — Cholesterin,  C.,^H,,0,  is  a  monatomic 
alcohol  that  is  normally  present  in  nervous  tissue,  blood- 
corpuscles,  bile,  and  elsewhere.  It  occurs  pathologically 
in  gall-stones,  as  well  as  in  atheromatous  cysts,  in  pus,  in 
tubercular  masses,  old  transudations,  excrements,  and 
tumors. 

Cholesterin  is  probably  not  a  constituent  of  the  urine 
in  health,  and  only  occurs  in  this  fluid  under  pathologic 
conditions.  It  crystallizes  in  large,  colorless,  transpar- 
ent plates  (Fig.  35),  whose  angles  and  sides  frequently 
appear  broken,  and  whose  acute  angles  are  often  from  jd 
to  87  degrees.     In  large  quantities  it  appears  as  a  mass 


CHOLESTERIN. 


229 


of  white  plates  having  a  luster  resembling  mother-of-pearl, 
and  a  greasy  feel. 

Cholesterin  is  insoluble  in  water,  dilute  acids,  and  alkalies. 
It  is  easily  soluble  in  boiling  alcohol,  and  recrystallizes 
on  cooling.  It  is  readily  soluble  in  ether,  chloroform, 
and  benzol,  and  also  in  the  volatile  and  fatty  oils.  It  is 
dissolved  to  a  slight  extent  b\^  alkaline  salts  of  the  bile 
acids.       > 

Cholesterin  crystals  are  only  found  in  the  urinary  sedi- 
ment in  cases  of  extensive  fatty  degeneration  of  some  part 
of  the  urinary  tract,  as,  rarely,  in  cases  of  subacute  glomer- 
ular nephritis  and  chronic  diffuse  nephritis,  and  still  more 
rarely  during  the  fatty  stage  of  an  acute  nephritis  ;  also  in 
case  of  the  evacuation  of  an  abscess  into  the  urinary  tract. 


Fis-  35- — Cholesterin  crystals. 


Detection. — If  a  mixture  of  five  parts  of  sulphuric  acid 
arid  one  part  of  water  acts  on  a  cholesterin  crystal,  first  a 
bright  carmine-red  and  then  a  violet  color  appears.  This 
fact  is  u.sed  in  the  microscopic  detection  of  cholesterin. 
Another  test  consists  in  treating  the  crystal  first  with  dilute 
sulphuric  acid  and  then  with  a  solution  of  iodine.  The 
cr\'stals  will  be  gradually  colored  violet,  bluish-green,  and 
finally  a  beautiful  blue. 

Sa/kcnvski' s  Reaction. — Cholesterin  is  dissolved  in  chloro- 
form, and  then  treated  with  an  equal  volume  of  concen- 
trated sulphuric  acid.  The  cholesterin  solution  becomes 
first  bluish-red,  then  gradually  violet-red,  while  the  sul- 
phuric acid  appears  dark  red  with  a  greenish  fluorescence. 

Cholesterin  is  readily  detected  in  the  urinary  sediment  by 
means  of  the  microscope. 


230  URINARY  SEDIMENTS. 

ORGANIZED  SEDIMENTS. 

The  organized  or  anatomic  sediments  consist  of  formed 
elements  coming  from  various  parts  of  the  urinary  tract. 
Some  of  these  elements  are  present  in  the  urine  under 
normal  conditions,  while  others  are  found  only  as  the  result 
of  functional  disturbance  or  disease. 

Blood. — Red  blood-corpuscles  in  the  urinary  sediment 
are  always  abnormal  constituents,  and  indicate  a  pathologic 
condition  in  some  portion  of  the  urinary  tract.  Not  infre- 
quently, in  the  female,  blood  enters  the  urine  from  the 
genital  tract  ;  under  such  circumstances  it  is  quite  unim- 
portant. 

Blood -corpuscles  vary  in  their  microscopic  appearance 
according  to  the  character  of  the  urine  in  which  they  are 
found,  the  length  of  time  they  have  been  in  the  urine,  and 
the  location  of  the  urinary  tract  from  which  they  come. 
Red  blood-corpuscles  are  conveniently  divided,  for  the  pur- 
pose of  urinary  examination,  into  two  classes — /.  c,  (a) 
normal  and  {li)  abiioniial  blood  globules. 

(a)  Normal  Blood. — This  refers  to  the  unaltered  blood- 
corpuscles,  which  are  so  characteristic  in  appearance  that 
there  is  very  little,  if  any,  danger  of  mistaking  them  for  other 
elements  in  the  sediment.  They  consist  of  biconcave  discs, 
which  ahuays  have  a  yellow  color.  (Fig.  36,  left  half)  They 
are  smaller  than  a  leucocyte,  being  about  g-^-Vo"  ^^  '^'^  '\nc\v 
(between  7  and  8  micromillimeters)  in  diameter,  free  from 
nuclei,  and  perfectly  homogeneous — that  is,  free  from  gran- 
ules and  other  visible  cell-contents.  These  biconcave  discs 
undergo  a  reversal  of  light  and  shadow  on  careful  focusing, 
the  center  and  periphery  alternating  in  brightness  or  shadow 
as  the  objective  is  approximated  to  the  slide  or  removed  from 
it.  Normal  blood  globules  that  have  been  in  the  urine  for 
some  time  begin  to  undergo  a  change.  Their  edges  often 
become  irregular  and  crenated, — the  so-called  crcnatcdblood- 
corpiisclc, — found  particularly  in  urines  that  contain  a  rela- 
tively large  proportion  of  sodium  chloride.  This  form  still 
has  more  or  less  color,  and  belongs  to  the  class  of  normal 
blood.  In  fact,  any  blood-corpuscle  that  has  the  slightest 
yellowish  tint  can  be  considered  a  normal  blood-corpuscle. 
Within  a  few  hours  after  the  blood  enters  the  urine  the  cor- 
puscle begins  to  swell  and  lose  its  color  and  density,  and 
it  is  then  that  we  have  the — 


BLOOD.  231 

(b)  Abnormal  Blood  Globules. — These  are  merely 
blood  rings  or  shadows.  (Fig.  36,  right  half.)  _  The  blood 
globule  that  was  formerly  biconcave  is  now  biconvex — in 
other  words,  is  swollen  and  has  become  a  sphere,  devoid  of 
color  or,  if  any  color,  the  slightest  tint  of  brown  at  the 
margin.  The  corpuscle  has  also  become  reduced  in  diam- 
eter, being  only  about  two-thirds  of  the  diameter  of  the 
normal  blood-corpuscle.  There  are  various  forms  of  cor- 
puscles in  the  change  from  normal  to  abnormal  blood,  but, 
since  the  color  is  the  criterion,  any  blood-corpuscle  that  has 
lost  its  yellow  color  is  abnormal. 

A  urine  containing  normal  blood  is  usually  more  or  less 
reddish  in  color,  depending  upon  the  quantity  present.  If 
the  amount  of  blood  is  excessive,  it  produces  in  alkaline 
urine  a  bright-red  color  (oxyhemoglobin),  and  in  highly 
acid  urine  more  of  a  brownish-red  color  (oxy-  and  methe- 


°     ^000 


o 


o        0 
o       C)     ° 

°        o 


o 


Fig.  36.— Blood-corpuscles :  a,  Normal;  6,  abnormal. 

moglobin).  Abnormal  blood,  when  present  in  considerable 
quantity,  imparts  a  brownish  or  smoky  color  (methemoglo- 
•bin  and  hematin)  to  the  urine.  If  present  in  large  amounts, 
the  color  is  usually  very  dark  and  may  be  black.  If 
the  quantity  of  either  normal  or  abnormal  blood  in  the 
.urine  be  small,  the  color  may  give  no  indication  of  its 
presence,  and  under  such  circumstances  is  not  usually  de- 
tected until  the  sediment  is  examined  microscopically. 

A  distinct  reaction  for  albumin  is  always  obtainable  in  a 
urine  containing  blood,  even  though  the  quantity  of  blood 
be  extremely  small. 

Treatment  of  a  Sediment  Containing  Blood. — The  presence 
of  a  large  amount  of  blood  in  the  urinary  sediment  gener- 
ally completely  obscures  other  formed  elements  ;  on  this 
account  the  blood  globules  must  be  destroyed.  The  de- 
struction of  blood  is  best  accomplished  in  the  following 
way : 


232  URINARY  SEDIMENTS. 

Allow  the  urine  to  settle  thoroughly  in  a  urine  glass,  then 
decant  the  supernatant  bloody  fluid,  and  to  the  sediment  re- 
maining in  the  glass  add  a  large  volume  of  lukewarm  water 
and  a  few  drops  of  dilute  acetic  acid.  Stir  thoroughly  with 
a  glass  rod,  breaking  up  all  clots,  and  allow  the  fluid  to 
settle  again.  Repeat  this  process  until  the  wash-water  is 
practically  free  from  blood  pigment.  Finally,  settle  and 
examine.  The  blood  pigment  will  be  found  to  have  been 
washed  from  the  blood-corpuscles,  leaving  a  very  fine  net- 
work of  abnormal  blood  globules  and  fibrin,  in  which  other 
formed  elements,  such  as  casts,  epithelium,  etc.,  are  capable 
of  detection. 

The  fact  that  a  urine  containing  a  large  quantity  of  blood 
always  contains  a  considerable  number  of  leucocytes  should 
be  borne  in  mind,  especially  in  drawing  inferences  as  to  the 
presence  or  absence  of  a  suppurative  process  that  is  associ- 
ated with  hemorrhage.  If  the  leucocytes  are  numerous — 
in  fact,  abundant — and  more  or  less  arranged  in  clumps, 
suppuration  in  some  part  of  the  urinary  tract  is  highly 
probable. 

"  Hematuria  "  is  the  term  applied  to  a  urine  that  contains 
blood, — that  is,  the  blood-corpuscles  together  with  the 
blood  pigment, — and  should  not  be  confounded  with  the 
term  "  hemoglobinuria,"  which  applies  to  a  urine  containing 
blood  pigment  witJiont  blood-corpuscles.      (See  p.  362.) 

Clinical  Significance. — The  first  interest  in  connection 
with  a  hematuria  is  to  locate  the  source  of  the  hemorrhage. 
Blood  in  the  urine  may  come  from  the  kidney,  pelvis  of 
kidney,  ureter,  bladder,  prostate,  or  urethra.  Blood  com- 
ing from  the  genital  tract  of  the  female  should  in  all  cases 
be  distinguished  from  that  coming  from  the  urinary  tract. 

From  the  Kidney. — In  fresh  urine  blood  from  the  kidney 
is  usually  abnormal  in  character,  and  therefore  imparts  a 
more  or  less  smoky  color  to  the  urine.  Such  urines  after 
standing  deposit  a  brown  or  coffee-colored  sediment.  But 
the  blood  may  be  normal,  especially  if  from  the  straight 
tubules  or  in  case  of  abundant  renal  hemorrhage  when  the 
urine  is  generally  of  a  bright-red  or  brownish-red  color,  and 
upon  standing  furnishes  an  abundant  blood-red  sediment. 
Urines  containing  blood  from  the  kidneys  are  generally 
acid  in  reaction,  although  if  the  amount  of  blood  be  very 
large,  the  reaction  may  be  alkaline.  Blood  from  the  kidney 
is  usually  accompanied  by  renal  casts,  which  often  have  the 


BLOOD.  233 

blood  adherent  ;  and  even  blood-casts  may  be  found.  This 
fact  constitutes  an  important  element  in  diagnosis,  since  the 
only  positive  evidence  of  renal  hemorrhage  is  the  presence 
of  blood  on  casts  and  true  blood-casts.  Blood-clots,  usually 
of  small  size,  are  not  infrequently  found  in  the  sediment  in- 
cases of  abundant  hematuria  of  renal  origin.  Large  clots, 
however,  are  generally  absent  from  the  sediment  unless  they 
be  of  the  long,  slender,  rod-like  variety,  which  have  been 
molded  in  passing  through  the  ureters.  In  case  the  hemor- 
rhage is  very  slight  blood-clots  are  usually  not  found  in  the 
sediment. 

The  most  frequent  causes  of  blood  from  the  kidney  are 
the  acute  diseases  and  disturbances  of  this  organ,  such  as 
active  hyperemia  (little  blood),  severe  active  hyperemia  (con- 
siderable blood),  and  acute  nephritis  (large  amount  of 
blood).  A  ve/y  small  amount  of  blood  is  sometimes  found 
in  the  various  chronic  diseases  of  the  kidney,  but  is  generally 
so  slight  that  it  is  unimportant.  In  all  of  the  above-men- 
tioned kidney  affections  the  blood  is  usually  abnormal.  In 
an  exacerbation  of  an  acute  or  an  acute  exacerbation  of  a 
chronic  kidney  disease  the  blood  is  generally  abundant  and 
normal  in  character,  this  condition  being  characterized  by 
the  sndden  appearance  of  normal  blood  and  a  rapid  fall  in 
the  twenty-four-hour  quantity  of  urine.  (See  p.  298.) 
This  form  of  renal  hemorrhage  is  most  common  in  the 
parenchymatous  forms  of  renal  disease,  such  as  acute 
nephritis,  subacute  glomerular  nephritis,  and  chronic  diffuse 
nephritis.  Hematuria  is  not  uncommon  in  chronic  inter- 
stitial nephritis  as  the  result  of  vascular  changes,  including 
cardiac  disease  and  atheromatous  arteries.  It  is  by  no 
means  rare  in  amyloid  infiltration  of  the  kidneys,  on  ac- 
count of  the  extensive  infiltration  about  the  smaller  blood- 
vessels. 

In  tuberculosis  of  the  kidney  hemorrhage  is  a  common 
symptom.  The  attacks  are  usually  intermittent,  although 
at  times  constant  for  a  long  period.  An  abundance  of  pus 
frequently  accompanies  a  hematuria  of  this  origin.  A  v&ry 
thorough  search  for  tubercle  bacilli  in  the  urinary  sediment 
should  always  be  made  before  eliminating  this  possibilit\' 
of  hemorrhage.  New  growths  of  the  kidney  also  give  rise 
to  repeated  attacks  of  hematuria,  and  at  times  the  quantity 
of  blood  is  profuse.  There  is  generally  more  or  less  pus  in 
the  sediment,  and  also  an  abundance  of  small   round  and 


234  URINARY  SEDIMENTS. 

degenerated  cells.  Such  cases  are  to  be  recognized  by- 
renal  tumor,  more  or  less  pain,  and  general  cachexia  of  the 
patient. 

A  calculus  in  the  substance  of  the  kidney  or  in  the  renal 
pelvis  of  the  kidney  is  a  frequent  cause  of  hemorrhage. 
The  blood  is  generally  accompanied  by  more  or  less  pus. 
There  is  usually  pain  in  the  region  of  the  affected  kidney, 
tenderness  on  deep  pressure,  and  pain  extending  down  the 
leg  or  into  the  testicle.  There  may  be  renal  colic  when 
there  is  a  small  stone  in  the  renal  pelvis,  the  blood  often 
being  accompanied  by  small  caudate  cells  from  the  super- 
ficial layer  of  the  pelvis.  In  the  light  of  these  symptoms  a 
hematuria  resulting  from  a  calculus  should  be  suspected. 
The  sediment  should  be  carefully  searched  for  crystalline 
deposits,  which  may  or  may  not  be  present. 

The  ingestion  of  certain  drugs  such  as  cantharides,  tur- 
pentine, as  well  as  certain  other  poisonous  substances,  may 
give  rise  to  renal  hematuria.  It  may  also  be  due  to  trauma 
involving  the  kidneys,  either  directly  as  by  wounds  or 
blows,  or  indirectly  from  concussion.  In  tropical  countries 
renal  hematuria  is  frequently  the  result  of  an  invasion  of  the 
kidney  by  a  minute  parasite — distoma  haematobium.  (See 
p.  267.)  Of  the  various  other  causes  of  hemorrhage  of  renal 
origin,  renal  embolism,  purpura  haemorrhagica,  hydatids, 
abscess,  and  cystic  disease  of  the  kidneys  may  be  mentioned. 

From  the  Lnver  Urinary  Passages. — Abundant  hemor- 
rhage from  the  bladder  is  not  uncommon,  and  is  most  liable 
to  be  the  result  of  one  of  three  abnormal  conditions — /.  c., 
vesical  calculus,  tuberculosis,  or  new  growth.  A  moderate 
amount  of  blood  usually  accompanies  all  acute  and  chronic 
inflammations  of  the  bladder.  Blood  from  the  bladder  is 
generally  normal  in  character,  but  if  present  in  small 
amounts,  may  be  abnormal,  particularly  if  the  urine  in 
which  it  is  contained  be  highly  acid  or  strongly  akaline.  The 
quantity  of  blood  may  be  so  abundant  as  to  cause  coagula- 
tion within  the  bladder  or,  as  is  more  frequent,  shortly  after 
the  urine  has  been  voided.  Blood-clots  are  more  common  in 
vesical  hematuria  than  in  other  forms  of  hemorrhage,  and 
are  invariably  associated  with  profuse  bleeding.  The  clots 
are  usually  small  and  irregular  in  shape,  but  may  be  large 
and  regular.  A  clot  in  the  bladder  may  completely  ob- 
struct the  outflow  of  urine.  Rarely,  long,  smooth,  cord- 
like blood-clots  are  passed  by  the  urethra.     One  instance 


BLOOD.  235 

of  this  was  observed  by  the  author,  the  clot  being  seventy- 
two  inches  in  length. 

Blood  of  vesical  origin  is  generally  accompanied  by  more 
or  less  pus,  and  in  cases  of  long-standing  cystitis  the  urine 
is  frequently  alkaline,  although  not  invariably  so.  For 
purposes  of  diagnosis  the  blood  must  be  destroyed  before 
microscopic  examination  is  undertaken,  and  then  a  search 
made  for  characteristic  cells  of  new  growth,  or  crystalline 
elements  ;  or  the  sediment  prepared,  and  carefully  examined 
for  tubercle  bacilli. 

Hemorrhage  from  the  neck  of  the  bladder  is  probably 
most  commonly  the  result  of  tuberculosis,  although  it  may 
be  due  to  various  other  pathologic  conditions  of  this  region. 
In  most  respects  it  resembles  hemorrhage  from  the  fundus 
of  the  bladder,  although  accompanied  by  symptoms  sug- 
gestive of  neck-of-bladder  trouble. 

Hematuria  of  urethral  origin  may  arise  from  traumatism, 
acute  gonorrhea,  urethral  chancre,  or  following  surgical 
operations  on  strictures  of  the  urethra.  The  blood  is  gen- 
erally normal  in  character,  and  precedes  the  flow  of  urine, 
and  also  oozes  from  the  meatus  between  the  acts  of  mic- 
turition. 

TeicJiniaiDi'  s  Test  for  Blood  Pigment. — In  the  application 
of  this  test  to  urine  it  is  necessary  to  coagulate  the  albu- 
min, which  carries  down  with  it  the  blood  pigment.  This  is 
best  accomplished  for  the  purpose  of  this  test  (i)  by 
strongly  acidulating  the  urine  with  acetic  acid,  and  then 
adding  a  saturated  solution  of  sodium  tungstate  also  acidu- 
lated with  acetic  acid.  Upon  heating  this  mixture  a  brown- 
ish precipitate  of  albumin  and  blood  pigment  is  obtained, 
which  is  collected  on  a  filter  and  dried.  (2)  The  albumin 
can  also  be  coagulated  by  boiling  the  urine,  which  has  been 
faintly  acidulated  with  acetic  acid,  as  described  on  page 
129.  This  precipitate  is  placed  on  a  filter,  washed,  and 
dried. 

Method. — A  small  portion  of  the  dried  and  powdered  pre- 
cipitate containing  the  blood  pigment  is  placed  on  a  micro- 
scopic slide,  and  moistened  with  a  weak  solution  of  potas- 
sium iodide  or  sodium  chloride,  and  evaporated  to  dryness. 
The  residue  is  covered  with  a  cover-glass,  and  glacial 
acetic  acid  allowed  to  flow  underneath  in  contact  with  the 
powder.  This  preparation  is  then  gently  heated  until  the 
acid    begins   to    boil,   when    it    is    cooled,    and    examined 


236  URINARY  SEDIMENTS. 

by  means  of  the  microscope.  If  blood  pigment  be  pres- 
ent, brown  rhombic  plates  (Fig.  ^y)  of  iodide  or  chh^ride 
of  hematin  (also  known  as  hemin  crystals)  will  be  found. 
These  rhombic  crystals  are  generally  isolated,  but  they 
occasionally  cross  each  other  to  form  more  or  less  charac- 
teristic groups. 

This  test  affords  one  very  important  means  of  determin- 
ing the  presence  of  blood  or  blood  pigment  in  the  urine 
and  other  fluids  of  the  body.  It  is  also  of  great  import- 
ance in  distinguishing  between  the  dark  or  black  urines  due 
to  hemoglobin  (see  Hemoglobinuria,  p.  362)  and  those 
that  are    dark   or  black   from  other  pigments.      Further- 


Fig.  37. — Teichmann's  hemin  cr>'Stals. 

more,  this  test  is  of  great  practical  value  in  the  medicolegal 
detection  of  blood. 

Pus. — Pus-corpuscles,  also  termed  leucocytes,  are  round, 
well-defined  bodies,  which  are  usually  extremely  gran- 
ular. (Fig.  38,  «.)  They  vary  a  little  in  size,  but  are 
usually  quite  constant  and  a  trifle  less  than  twice  the  size  of 
the  average  normal  blood  globule.  Although  generally 
round,  they  vary  somewhat  in  shape  according  to  the  age 
of  the  pus,  the  reaction  of  the  urine,  and  the  pathologic 
process  that  they  accompany.  Pus-corpuscles  usually  con- 
tain two  or  three  nuclei, — polymorphonuclear  leucocytes, 
— which  constitute  the  chief  characteristic  of  the  typical 
pus-corpuscle.  There  is  also  the  moiiomiclcar  leucocyte, 
which  is  less  common  in  the  urinary  sediment,  and  not 
easily  distinguished  from  the  small  round  cell. 


PUS.  237 

The  nuclei  of  the  pus-corpuscle  are  not  usually  distinct, 
on  account  of  the  very  granular  character  of  the  body,  but 
if  the  corpuscle  be  not  decomposed  or  disintegrated,  two 
or  more  nuclei  can  be  made  out  upon  focusing  closely. 
The  distinctions  of  the  nuclei,  and,  in  fact,  the  general 
appearance  of  the  pus-corpuscle,  depend  largely  upon  the 
reaction  of  the  urine  in  which  they  are  contained  and  the 
age  of  the  pus. 

In  Acid  Urine. — Fresh  pus  in  an  acid  urine  is  very 
dense  and  the  nuclei  are  seen  with  difficulty,  if  at  all  ;  this 
constitutes  the  so-called  "  normal  pusy  On  the  other 
hand,  pus  which  has  been  suspended  in  the  urine  for  some 
period,  either  within  or  outside  the  body,  has  a  different 
appearance  ;  the  body  of  the  corpuscle  becomes  less  distinct 
and  the  nuclei  more  prominent ;  this  is  sometimes  termed 


®    ®    ® 


® 
© 


Fig.  38— a,  Pus-corpuscles  as  ordinarily  seen  ;  3,  ameboid  pus-corpuscles  ;  c,  pus-cor- 
puscles showing  the  action  of  acetic  acid. 


^' abnormal  pus''  or '' %vaslied-oiit  pits."  In  the  abnormal 
pus-corpuscle  the  nuclei,  instead  of  being  separate  bodies, 
are  often  fused,  forming  a  single  horseshoe-shaped  nucleus, 
.which  is  not  so  dense  as  the  individual  nuclei  of  the  nor- 
mal pus-corpuscle.  These  abnormal  pus-corpuscles  may 
come  from  any  part  of  the  urinary  tract,  and  are  most  com- 
mon in  cases  of  long-continued  chronic  inflammation. 

In  Alkaline  Urine. — When  a  urine  containing  pus  be- 
comes alkaline  by  a  volatile  alkali  or  alkaline  hydrate,  such 
as  ammonium  carbonate  or  hydrate  resulting  from  the 
decomposition  of  the  urea,  the  pus-corpuscles  become  de- 
stroyed. By  the  action  of  the  alkali  the  pus  becomes 
converted  into  a  gelatinous,  tenacious  mass  (see  Donne's 
Test  for  Pus),  which  in  many  respects  resembles  white  of 
&%g.      If  a  portion  of  this  mass  be  examined   microscopi- 


238  URINARY  SEDIMENTS. 

cally,  the  pus-corpuscles  will  be  found  to  have  been  de- 
stroyed, while  only  a  dense  mucus-like  mass  with  adherent 
amorphous  phosphates,  crystals  of  triple  phosphate,  and 
bacteria  remains.  Some  of  the  nuclei  of  the  pus-corpus- 
cles may  still  be  found. 

Pus-corpuscles  are  practically  indentical  with  the  white 
corpuscles  of  the  blood  and  lymph.  In  a  fresh  state  they 
often  present  protoplasmic  processes, — ameboid  move- 
ments,— and  under  such  circumstances  should  not  be  mis- 
taken for  small  caudate  cells. 

It  is  very  important  to  determine  the  exact  nature  of  all 
small,  round,  or  irregular  bodies  whose  nuclei  are  not  dis- 
tinct, to  distinguish  between  leucocytes  and  small  round 
cells,  and  also  between  ameboid  leucocytes  and  small  cau- 
date cells.  This  is  best  accomplished  by  treating  the  urin- 
ary sediment  with  dilute  acetic  acid,  as  follows  :  Moisten 
the  microscopic  slide  with  a  fraction  of  a  drop  of  the  acid, 
then  place  a  drop  of  the  sediment  on  the  drop  of  acid  ; 
mix  thoroughly  by  means  of  a  glass  rod,  and  cover  with 
a  cover-glass. 

Action  of  Acetic  Acid. — When  dilute  acetic  acid  (20  per 
cent.)  is  added  to  a  fluid  containing  pus,  the  changes  in  the 
corpuscles  are  very  rapid  ;  the  first  effect  being  to  cause  them 
to  swell  up,  and  next  to  dissolve  the  granules,  the  body  of 
the  corpuscle  becoming  smooth  and  the  nuclei  very  distinct. 
In  a  short  space  of  time  the  body  of  the  corpuscle  becomes 
almost  invisible,  while  the  nuclei  remain  a  much  longer 
time. 

Epithelial  cells  are  affected  by  acetic  acid  in  much  the 
same  manner  as  leucocytes,  but  to  a  less  marked  degree. 
The  first  effect  is  a  solution  of  the  granules,  making  the 
nucleus  very  prominent,  and,  finally,  after  prolonged  action 
of  the  acid,  the  cell  begins  to  swell.  The  body  of  the  cell 
does  not  usually  become  faint  or  invisible  by  the  action  of 
this  acid. 

The  action  of  water  on  the  pus-corpuscle  and  epithelial 
cell  is  identical  with  that  of  acetic  acid,  except  that  it  is 
very  much  slower  and  the  stage  of  distinct  nuclei  is  reached 
much  later. 

Characteristics  of  Uri)ie  Containing  Pits. — An  acid  urine 
containing  pus  is  turbid  except  when  the  corpuscles  are 
only  few  in  number.  It  very  soon  deposits  an  opaque 
white  sediment,  which  rapidly  settles  to  the  bottom  of  the 


PUS.  239 

sediment  glass.  This  deposit  should  not  be  mistaken  for  a 
deposit  of  amorphous  urates  or  phosphates.  The  distinc- 
tion is  easily  made  by  means  of  the  microscope,  also  by 
the  fact  that  the  phosphatic  deposit  is  readily  dissolved  by 
acetic  acid,  while  the  deposit  of  pus  undergoes  the  changes 
already  described.  On  the  other  hand,  a  deposit  of  amor- 
phous urates  is  readily  dissipated  by  gentle  heat. 

A  purulent  urine  that  has  undergone  alkaline  fermenta- 
tion is  invariably  turbid  and  often  contains  a  large,  ropy 
mass,  consisting  of  decomposed  pus,  etc.,  as  previously 
mentioned. 

Donne' s  Test  for  Pus. — This  depends  upon  the  reaction 
that  takes  place  between  alkalies  and  the  pus,  and  consists 
in  the  addition  of  an  alkaline  hydrate — potassic,  sodic,  or 
ammonic  hydrate — to  the  suspected  urine,  or  its  sediment 
after  the  supernatant  urine  has  been  poured  off.  If  pus 
be  present,  the  urine  becomes  viscid,  or  the  sediment  is 
promptly  converted  into  a  viscid,  gelatinous,  mucus-Hke 
mass,  which  adheres  to  the  bottom  and  sides  of  the  test- 
tube.  If  some  of  this  viscid  substance  be  examined  under 
the  microscope,  the  pus-corpuscles  will  be  found  to  have 
been  destroyed  or,  rather,  converted  into  the  substance  it- 
self. If  the  action  has  not  been  very  long  or  the  propor- 
tion of  the  alkali  to  the  pus  is  small,  the  outline  of  the  pus- 
corpuscles  may  still  be  seen  ;  so,  also,  the  nuclei  of  the 
corpuscles  may  still  be  discernible,  embedded  in  the  mucus- 
like mass. 

According  to  v.  Jaksch,  leucocytes  are  stained  a  deep 
rhahogony-brown  (glycogenic  reaction)  by  a  solution  of 
potassic  iodide.  This  serves  to  distinguish  them  from 
small  round  cells,  which  are  stained  a  light  yellow  color. 
'  A.  Vitali  recommends  the  following  test  for  pus  :  The 
suspected  urine,  if  alkaline,  is  acidulated  with  acetic  acid, 
and  filtered  through  a  thick  filter.  The  deposit  on  the 
filter  is  then  treated  with  a  little  guaiacum  tincture,  which 
has  been  kept  in  the  dark.  If  pus  be  present,  the  inner 
surface  of  the  filter  takes  a  blue  tint.  The  result  is  ob- 
tained even  with  a  small  number  of  leucocytes. 

Clinical  Significance. — A  perfectly  normal  urine  may  con- 
tain isolated  leucocytes.  It  is  only  when  they  occur  in 
considerable  numbers  or  in  conjunction  with  other  formed 
elements  (casts,  etc.)  that  their  presence  becomes  important. 

Pus  is  one  of  the  most  common  elements  found  in  the 


240  URINARY  SEDIMENTS. 

urinary  sediment.  It  may  be  derived  from  the  .sub.stancc  of 
the  kidney  or  pelvis  of  the  kidney,  the  ureters,  the  bladder, 
the  prostate  gland,  the  urethra,  or  from  the  rupture  of  an 
abscess  into  some  part  of  the  urinary  tract.  Given,  then,  a 
urine  containing  pus,  the  first  effort  should  be  directed 
toward  determining  its  source.  The  character  of  the  ele- 
ments (cells,  casts,  etc.)  that  accompany  the  pus  is  of  the 
utmost  importance  in  locating  the  suppurative  process. 

Pus  coming  from  the  kidney  is  found  in  cases  of  chronic 
suppuration  in  the  tulnilcs,  such  as  may  result  from  the 
presence  of  a  calculus,  the  existence  of  a  tubercular  pro- 
cess, or  the  extension  of  an  inflammation  from  the  pelvis 
of  the  kidney  into  the  renal  tubules.  In  these  conditions 
the  pus  is  usually  present  in  large  quantity,  and  is  some- 
times accompanied  by  a  few  or  numerous  renal  casts, 
including  pus-casts,  which  come  from  the  suppurating  area 
or  the  neighborhood  of  the  diseased  area  in  the  kidney.  In 
acute  nephritis  and  following  acute  exacerbations  of  chronic 
renal  diseases  pus  is  usually  present  in  greater  or  smaller 
quantities,  and  often  found  adherent  to  casts,  but  in  these 
conditions  true  pus-casts  are  only  rarely  found. 

The  diagnosis  of  abscess  of  the  kidney  can  not  be  posi- 
tively determined  until  the  abscess  has  evacuated  its  con- 
tents into  the  urinary  passages.  Previous  to  rupture  of 
the  abscess  the  urine  usually  presents  evidences  of  a  renal 
congestion — active  hyperemia — that  is  going  on  in  the  renal 
tissue  around  the  abscess  pocket.  A  urine  that  suddenly 
contains  a  large  quantity  of  greenish  pus  strongly  suggests 
abscess  of  the  kidney. 

In  chronic  pyelitis  the  urine  is  generally  acid  in  reaction  ; 
the  pus  is  not  only  free,  but  is  often  arranged  in  clumps,  and 
is  mixed  with  small  round  cells  from  the  deep  layer  of  the 
pelvis  of  the  kidney.  Any  obstruction  to  the  outflow  of 
pus  causes  a  pyonephrosis  ;  if  the  back  pressure  becomes 
sufficient  to  force  an  opening,  a  sudden  gush  of  greenish 
pus  follows.  So  far  as  the  author  is  aware  an  abundant 
deposit  of  greenish-colored  pus  is  indicative  only  of  abscess 
of  the  kidney,  the  evacuation  of  an  abscess  into  the  urinary 
tract,  or  pyonephrosis. 

Numerous  leucocytes  usually  accompany  an  acute  pye- 
litis, but  ordinarily  they  are  insignificant  as  compared  with 
the  other  formed  elements,  which  are,  in  themselves,  diag- 
nostic. 


EPITHELIUM.  241 

Acute  and  chronic  inflammations  of  the  bladder — cystitis 
— are  always  associated  with  purulent  urine.  In  acute  cys- 
titis the  urine  is  generally  acid,  but  in  chronic  inflammation 
of  this  membrane  the  urine  is  often  alkaline — ammoniacal 
— when  voided.  This  is  by  no  means  true  of  every  chronic 
inflammation  of  the  bladder,  since  in  tubercular  cystitis  and 
also  in  some  cases  of  calculous  cystitis  the  urine  is  acid  in 
reaction.  Purulent  urines  in  general,  and  especially  those 
from  the  bladder,  readily  become  alkaline  upon  standing 
exposed  to  the  air,  if  not  already  alkaline  when  voided.  In 
cystitis  the  ropy,  glairy  mass  consisting  of  decomposed  pus, 
amorphous  and  crystalline  phosphates,  as  well  as  epithelial 
cells,  is  not  infrequently  found. 

Pus  from  the  neck  of  bladder  or  prostatic  region  is  often 
found  free,  and  arranged  in  clumps  and  mixed  with  neck- 
of-bladder  cells.  Oftentimes  spermatozoa  are  found  free 
and  mixed  with  the  pus  in  shreds. 

In  urethritis  the  pus  is  usually  very  dense,  and  found 
chiefly  in  long  threads  or  shreds,  mingled  with  urethral 
cells,  especially  when  of  gonorrheal  origin.  When  the 
amount  of  pus  is  abundant,  it  is  generally  free,  no  shreds 
being  found.  In  acute  gonorrhea  the  pus  is  usually  yel- 
lowish in  color.  If  any  doubt  exists  as  to  the  exact  source 
of  this  pus,  the  question  is  often  settled  by  directing  the 
patient  to  pass  the  first  portion  of  his  urine  into  one  ves- 
sel and  the  last  portion  into  another  ;  if  urethral,  the  first 
portion  will  contain  much  pus,  while  the  second  will  be 
practically  free  from  it. 

-  Pus  from  the  uterus  or  vagina  is  usually  accompanied  by 
an  abundance  of  squamous  epithelium.  If,  in  the  case  of 
a  female,  there  is  any  doubt  as  to  the  source  of  the  epi- 
thelium and  pus, — whether  bladder  or  vaginal, — a  catheter 
specimen  or  one  voided  after  a  thorough  vaginal  douche 
should  be  procured.  If  pus  be  present  in  such  a  specimen, 
it  must  have  originated  in  some  portion  of  the  urinary  tract ; 
but  if  no  pus  be  present,  then  it  must  have  come  from  the 
genital  tract.  In  blennorrhea  a  considerable  quantity  of  pus 
may  find  its  way  into  the  urine. 

Epithelium. — Epithelial  cells  from  various  parts  of  the 

urinary  tract  usually  form  a  part  of  the  sediment  of  every 

normal   and  pathologic  urine.     Epithelium  is  the  normal 

product    of  the    mucous    membrane,    and    represents    the 

"  wear  and  tear  "  of  such  surfaces.      In  disease  the  desqua- 
i6 


242  URINARY  SEDIMENTS. 

mation  is  usually  much  increased  ;  the  recognition  of  the 
cells  from  the  various  parts  of  the  urinary  passages  is, 
therefore,  of  the  greatest  importance,  for  it  is  often  only  by 
this  means  that  abnormal  processes  can  be  located.  The 
student  should  familiarize  himself,  as  far  as  possible,  with 
the  cells  that  are  characteristic  of  certain  areas,  before 
drawing  inferences  as  to  pathologic  states  ;  he  should  also 
bear  in  mind  that  every  normal  urine  contains  a  certain 
number  of  cellular  elements. 

The  epithelial  cells  found  in  the  urinary  sediment  coming 
from  a  given  part  of  the  tract  usually  have  entirely  different 
shapes  from  those  found  in  prepared  histologic  specimens 
of  that  part.  For  example,  some  of  the  renal  epithelium 
///  situ  is  cuboid  in  shape,  while  that  found  in  the  urine  is 
usually  round.  Other  similar  examples  could  be  cited  in 
which  the  shapes  of  the  original  cells  have  become  changed, 
apparently  by  the  action  of  the  urine. 

In  the  detailed  study  of  the  cells  that  follows,  the 
leucocyte  ivill  be  used  as  a  standard  for  comparison,  since 
this  body  is  nearly  constant  in  size.     (Fig.  39,  a.) 

Renal  Epithelium. — These  are  epithelial  cells  from  the 
tubules  of  the  kidney.  They  are  essentially  small  round 
cells,  which  are  usually  more  or  less  granular,  and  present 
a  single  nucleus.  (Fig.  39,  b.^  There  are  three  sizes  of 
renal  cells  :  /.  ^.,  the  first,  which  is  smaller  than  a  leucocyte, 
and  probably  comes  from  the  smaller  tubules  in  the  cortical 
portion  of  the  kidney  ;  the  second,  which  is  about  the  same 
size  as  the  leucocyte,  and  constitutes  the  average  renal  cell, 
which  is  probably  from  the  convoluted  tubules  ;  and  the 
third,  which  is  larger  than  the  leucocyte,  and  probably  comes 
from  the  straight  or  collecting  tubules.  Renal  cells  are 
frequently  adherent  to  casts  and,  when  practically  covered 
with  them,  form  the  so-called  epithelial  cast.  Renal  cells 
are  often  very  granular,  and  sometimes  much  distorted,  as  a 
result  of  degenerative  processes  in  the  kidney  ;  such  are 
seen  especially  in  cases  of  advanced  chronic  interstitial 
nephritis. 

Fatty  renal  cells  ^XQ  those  which  contain  fat-drops  (Fig. 
39,  <?),  and  are  the  result  of  degenerative  processes  in  the 
tubules  of  the  kidney.  Such  cells  may  contain  only  one  or 
two  fat-globules,  or  they  may  be  entirely  fatty  degenerated. 
They  do  not  usually  differ  in  size  from  the  renal  cells 
already   mentioned,  and   are   not   to   be   mistaken   for  the 


PELVIC  EPITHELIUM.  243 

larger,  so-called  compound  granule  cell,  to  be  described 
later.  Not  infrequently  some  or  all  of  the  fat  is  washed 
out  of  the  cell,  when  it  will  be  found  to  contain  one  or  more 
vacuoles.  Fatty  renal  cells  are  found  in  the  urinary  sedi- 
ment in  cases  of  subacute  glomerular  nephritis,  chronic 
diffuse  nephritis,  during  the  fatty  stage  of  acute  nephritis, 
and  not  infrequently  in  the  severer  forms  of  renal  congestion.' 
Renal  cells  always  accompany  renal  casts,  although  at 
times  they  are  present  only  in  small  numbers.  Any  small 
round  cell  that  is  adherent  to  a  cast  can  be  safely  considered 
a  renal  epithelial  cell. 

Pelvic  Epithelium. — Epithelial  cells  from  the  pelvis  of 
the  kidney  vary  in  shape  according  to  the  parts  from  which 
they  come,      (a)    Those  from  the  supa-jicial  layer  of   the 
pelvis  are  small  caudate  cells.     (Fig.  39,  c.)     The  tails  are 
often  curved  and  at  times  are  bifurcated.      The  body  is  the 
same  size  or  perhaps  a  little  larger  than  that  of  the  leuco- 
cyte,  and   usually  has  a  distinct   nucleus,  a   brown  color, 
and  is  quite  granular.     These  cells  are  sometimes  arranged 
in  groups,  overlapping  "like  shingles  on  a  roof,"   but  are 
usually  found   singly.      They   are    invariably  accompanied 
by  more  or  less  blood,  and  indicate  either  a  simple  irritation 
of  the  renal  pelvis  or  a  more  extensive  inflammatory  process 
— an  acute  pyelitis.      They  are  of  frequent  occurrence,  and 
often  occur  in  very  large  numbers  in  cases  of  acute  pyelo- 
nephritis, especially  those  cases  that  are  of  toxic  origin.      (/;) 
The   cells  from   the  deep  layer  of  the  pelvis  of  the  kidney 
are  merely  small  round  cells  (Fig.  39,  d),   usually  about  • 
the  size  of  the  leucocyte,  and  having  much  the  same  appear- 
ance as   the  renal  cells,  although  frequently  not  quite  so 
dense.     These  cells  are  often  arranged  in  clumps,  and  are 
always  accompanied  by  pus  which   is  both  free  and  mixed 
with   the   cells   in    clumps.      Deep  pelvic  cells  are  always 
found  in  cases  of  chronic  pyelitis.     (.)  The  cells  from  the 
caliccs  of  the  kidney  (Fig.  39,  e)  are  only  rarely  found  in  the 
sediment.     They  belong  to  the  class  of  small  round  cells, 
but  are  considerably  larger  than  the  deep  pelvic  cells.      They 
are  also  somewhat  larger  than  the  cells  from   the  straight 
tubules  of  the  kidney,  and  are  generally  found  in  clunips, 
overlapping  one  another.     These  cells  have  large,  roundi 
prominent  nuclei,  and  are  less  granular  than  the  cells  from 
the  deeper  layer  of  the  pelvis.      They  are  usually  found  in 
cases  of  acute  pyelitis. 


244 


URINARY  SEDIMENTS. 


Ureteral  Epithelium. — The  author  has  had  exceptional 
opportunities  for  the  study  of  cells  from  the  ureter  in  speci- 
mens obtained  by  the  ureteral  catheter.  EpitheHal  cells 
from  the  ureter  are  of  two  forms  (Fig.  39,/) — i.  e.,  (i) 
small  caudate  cell,  which  is  somewhat  larger  and  denser 
than  the  cell  from  the  superficial  layer  of  the  pelvis  of  the 
kidney,  also  with  a  larger  and  more  prominent  nucleus  and 
a  somewhat  larger  tail ;  and  (2)  a  small  spindle  cell,  which 
is  generally  very  narrow  and  with  a  small  nucleus.  These 
two  forms  of  cells  are  usually  quite  granular  and  small,  and 


Fig.  39. — Epithelium  from  various  parts  of  the  urinary  tract :  a,  Leucocyte  (for 
comparison);  b,  renal  cells;  c,  superficial  pelvic  cells;  rf,  deep  pelvic  cells;  ^,  cells 
from  calices  ;  /",  cells  from  ureter  ;  g,  g,  g,  g,  g,  squamous  epithelium  from  the  blad- 
der ;  h,  /i,  neck-of-bladder  cells  ;  z,  epithelium  from  prostatic  urethra  ;  k,  urethral  cells ; 
/,  /,  scaly  epithelium  ;  m,  m',  cells  from  seminal  passages  ;  n,  compound  granule  cells  ; 
o,  fatty  renal  cell. 


should  not  be  confounded  with  similar  cells  of  larger  size, 
which  come  from  the  bladder.  The  diagnosis  of  an  inflam- 
matory process  in  the  ureter  is  generally  not  easily  made 
from  the  urinary  sediment,  since  the  number  of  cellular 
elements  from  this  membrane  is  often  small,  and  the  in- 
flammatory condition  is  usually  accompanied  by  either  a 
pyelitis  or  a  cystitis.  In  case  there  is  marked  irritation  of 
the  mucous  membrane  of  the  ureter  by  crystalline  elements 
or  small  calculi,  ureter  cells  may  be  found  in  large  numbers, 
and  the  diagnosis  more  easily  determined. 


BLADDER  EPITHELIUM.  245 

Bladder  Epithelium. — The  epithelial  cells  from  the 
fundus  of  the  bladder  are,  for  the  most  part,  of  the  squamous 
or  pavement  variety.  They  are  large,  flat,  thin,  polygonal 
cells  (Fig.  39,  g),  having  a  distinct  and  usually  a  central 
nucleus,  which  is  prominent  without  the  aid  of  acetic  acid. 
When  arranged  in  groups,  the  cells  are  frequently  found 
joined  by  their  edges  and  not  overlapping,  although  at  times 
they  are  found  overlapping  to  a  slight  extent.  Squamous  cells 
from  the  bladder  are  generally  moderately  granular,  but  may 
be  entirely  free  from  granules.  Those  cells  that  come  from 
near  the  openings  of  the  ureters  are  usually  large,  thin,  and 
circular  in  shape.  Epithelial  cells  from  the  month  are  not 
unlike  those  from  the  fundus  of  the  bladder,  but  differ  by 
having  small  nuclei  and  containing  small  particles  of  carbon. 
Cells  from  the  mouth  are  generally  clumped,  and  accom- 
panied by  a  large  amount  of  mucin  in  which  they  are  en- 
tangled, and  often  by  particles  of  food. 

Epithelial  cells  from  the  neck  of  the  bladder  (in  the  male) 
are  thicker,  smaller,  and  much  denser  than  those  coming 
from  the  fundus.  They  are  generally  round  or  oval,  and 
have  a  small,  prominent  nucleus.  (Fig.  39,  h.)  They  are 
usually  not  granular,  and  are  from  three  to  five  times  the 
size  of  a  leucocyte.  Cells  from  the  neck  of  the  bladder 
are  often  arranged  in  clumps  of  three  or  five,  but  are  usually 
not  found  overlapping.  An  occasional  cell  from  this  region 
may  be  found  in  a  perfectly  healthy  urine,  but  when  found 
in  excess  with  leucocytes,  they  indicate  an  irritation,  and 
when  mixed  with  pus.  an  inflammatory  process  at  the  neck 
of  the  bladder. 

Prostatic  Cells. — Epithelial  cells  from  the  prostatic 
ducts  are  small  round  cells,  which  are  not  unlike  renal  cells 
in-  size.  They  are  usually  less  granular  and  somewhat 
denser  than  renal  cells,  and  present  a  single  distinct  nucleus. 
They  are  often  adherent  to  long  shreds  of  mucin, — so-called 
"prostatic  casts,'' — and  are  generally  accompanied  by  leuco- 
cytes and  often  by  spermatozoa. 

Seminal  Cells. — These  are  cells  from  the  seminal 
passages,  and  are  medium  round  cells,  which  are  highly 
granular,  rather  dense,  and  contain  an  ill-defined  nucleus. 
(Fig.  39,  ;;/,  ;//.)  Spermatozoa  are  often  found  within  the 
body  of  the  cell  or  projecting  from  it.  These  cells  are  in- 
variably accompanied  by  free  spermatozoa. 

Urethral  Cells. — Epithelial  cells  from  the  urethra  vary 


246  URINARY  SEDIMENTS. 

in  shape  according  to  the  portion  from  which  they  come. 
Those  from  the  prostatic  portion  are  usually  dense,  pyriform, 
round,  or  irregular  cells  with  a  single  distinct  nucleus. 
(Fig.  39,  /.)  They  are  smaller  than  those  from  the  neck  of 
the  bladder,  and  from  one  and  one-half  to  twice  the  size  of 
a  leucocyte.  They  are  usually  not  clumped  unless  en- 
tangled in  shreds  of  mucin  with  pus,  as  is  often  the  case  in 
stricture  of  this  portion  of  the  urethra.  Cells  from  the 
pendulous  portion  of  the  urethra  are  either  small  round  or 
small  caudate  in  shape  (Fig.  39,  k),  but  somewhat  denser 
than  renal  and  superficial  pelvic  cells,  but  not  so  dense  as 
those  from  the  prostatic  urethra.  These  cells  are  most 
frequently  seen  in  the  discharge  that  results  from  a  gonor- 
rheal inflammation,  and  are  usually  intimately  mixed  with 
mucin  and  pus.  The  recognition  of  the  cells  from  this 
portion  of  the  urethra  is  of  no  great  consequence,  as  the 
diagnosis  of  a  urethritis  is  generally  made  by  other  means. 

Vaginal  Epithelium. — The  urine  of  the  female  nearly 
always  contains  more  or  less  epithelium  from  the  genital 
tract — that  is,  the  vaginal  secretion,  generally  consisting 
chiefly  of  epithelium  with  a  greater  or  smaller  number  of 
pus-corpuscles,  is  washed  from  the  vulva  and  often  causes 
a  very  abundant  sediment.  Vaginal  epithelium  consists 
chiefly  of  the  squamous  or  pavement  form,  although  many 
other  varieties  of  cells  are  usually  present,  such  as  the  spin- 
dle, large  and  medium  round,  large  and  small  caudate,  and 
irregular  cells.  These  cells  are  mononuclear,  and  usually 
only  slightly  granular,  and  generally  somewhat  larger  than 
the  average  sized  bladder  cell.  Vaginal  cells  are  often 
arranged  in  large  clumps,  and  on  careful  focusing  will  be 
found  to  be  overlapping,  "  like  shingles  on  a  roof,"  and  often 
several  layers  in  depth.  Very  often  the  so-called  scaly  epi- 
thelial cell  (Fig.  39,  r)  is  found,  which  represents  the  old 
epithelium  from  the  vulva,  and  is  a  very  thin,  degenerated 
cell,  containing  only  a  remnant  of  a  nucleus,  if  any  nucleus 
at  all.  A  urine  holding  a  large  amount  of  squamous  epi- 
thelium and  only  a  few  leucocytes  generally  contains  a 
vaginal  secretion,  which,  in  the  majority  of  instances,  is  not 
abnormal. 

Compound  Granule  Cells. — These  are  medium  and 
large  round  cells  that  have  undergone  complete  fatty  degen- 
eration. They  are  entirely  filled  with  fat  globules  of  vary- 
ing size,  and  do  not  show  a  nucleus.     (Fig.  39,  ;/.)     Com- 


RENAL  CASTS.  247 

pound  granule  cells  should  not  be  mistaken  for  fatty  renal 
cells,  the  former  being  always  larger  than  the  latter,  and 
usually  more  completely  degenerated.  Not  infrequently 
they  have  prismatic  or  long  hair-like  crystals  of  the  fatty 
acids  protruding  from  them.  They  may  be  found  free  in 
the  sediment,  or  adherent  to  casts.  Compound  granule 
cells  are  the  result  of  extensive  fatty  degeneration,  and 
come  not  only  from  the  urinary  tract  but  from  other  mucous 
membranes  as  well,  especially  those  that  are  chronically 
diseased.  When  of  renal  origin,  they  are  found  in  the 
sediment  during  the  fatty  stage  of  an  acute  nephritis,  also 
in  subacute  glomerular  and  chronic  diffuse  nephritis,  and 
rarely  in  active  hyperemia.  They  may  be  found  in  the 
sediment  in  chronic  pyelitis,  chronic  cystitis,  chronic  pros- 
tatitis, and  in  urethritis  ;  also  as  a  result  of  ulcerations  in  any 
part  of  the  urinary  tract,  and  often  in  large  numbers  in  the 
contents  of  an  abscess  or  cyst  cavity  that  has  evacuated 
into  the  urinary  passages.  They  are  sometimes  found  in 
vaginal  secretions,  and  also  in  expectorated  matter  that  has 
been  introduced  into  the  urine.  Compound  granule  cells 
are,  therefore,  of  no  great  practical  importance  unless  found 
in  the  presence  of,  and  adherent  to,  renal  casts. 

Renal  Casts. — Renal  casts,  also  termed  "tube-casts" 
and  "cylinders,"  are  molds  of  the  uriniferous  tubules. 
They  are  produced  by  the  admission  into  the  tubules  of  a 
coagulable  (?)  substance,  which  there  solidifies,  and,  en- 
tangling whatever  it  may  have  surrounded  in  its  liquid 
state,  subsequently  contracts,  and  is  forced  from  the  renal 
tubules  by  the  urine.  It  is  then  carried  into  the  pelvis  of 
the  kidney,  thence  into  the  bladder,  and  voided  with  the 
urine. 

The  origin  of  renal  casts  has  been  the  subject  of  much 
discussion  and  must  still  be  considered  an  unsettled  question. 

Three  theories  have  been  advanced  as  to  their  probable 
nature  and  mode  of  formation  : 

(«)  That  they  are  composed  of  coagulable  elements  of 
the  blood  that  have  transuded  into  the  renal  tubules  through 
pathologic  lesions  of  the  latter,  and  have  there  solidified, 
to  be  later  voided  with  the  urine  as  molds  of  the  tubules. 

{b')  That  they  consist  of  a  secretion  of  the  pathologic 
epithelium  lining  the  renal  tubules,  this  secretion  solidifying 
to  form  molds  or  tube-casts,  which  are  forced  out  by  the 
urine. 


248  URINARY  SEDIMENTS. 

(r)  That  they  are  the  direct  result  of  the  disintegration 
of  the  renal  cells,  whose  products  become  formed  into  casts 
of  the  tubules  in  which  they  are  formed,  and  being  forced 
out  by  the  urine  make  their  appearance  in  the  sediment. 

The  first  theory  {a)  is  the  most  plausible  of  the  three  ; 
at  least,  it  is  applicable  to  the  nature  and  mode  of  formation 
of  most  of  the  casts  found  in  the  urinary  sediment. 

Renal  casts  have  been  variously  classified,  but  the 
simplest  division  is  the  following,  which  is  based  upon  their 
microscopic  appearance  : 


I.   Hyaline  (transparent)  casts-/  (2 

1(3 


Pure  hyaline. 

Fibrinous. 

Waxy. 

Fine. 

Coarse. 

Brown. 


II.   Granular  "     < 

III.  Epithelial 

IV.  Blood 
V.   Fatty 

VI.   Pus 

r(i)  Urate. 
VII.   Crystalline  "     <  {2)  Oxalate. 

I  (3)  Cystin. 
VIII.  Bacterial 
IX.   "  Mucous "    (nucleo-albumin)  casts,   also    termed 
fa/si'  casts. 

I.  Hyaline  Casts. — Hyaline^  casts  are  of  three  varie- 
ties :  (i)  Pure  hyaline,  (2)  fibrinous,  and  (3)  waxy  casts. 

(/)  Pure  liyaline  casts  are  pale,  transparent,  homogeneous 
cylinders,  generally  with  rounded  ends.  (Fig.  40.)  They 
may  be  short  or  very  long,  even  extending  through  six  or 
more  fields  of  the  microscope.  ^  They  are  found  of  vary- 
ing diameters,  some  narrow  and  others  wide,  but  always 
presenting  a  cylindric  appearance.  Their  sides  are  usually 
parallel  and  straight,  but  they  may  be  indented,  presenting 
a  scalloped  appearance.  They  are  often  twisted  upon  them- 
selves, and  not  infrequently  have  a  serpentine  shape.  One 
end  of  the  cast  may  be  ragged  and  irregular,  showing  that 
the  original  cylinder  has  been  divided,  and  occasionally  a 

^  The  term  hyaline  is  here  used  in  the  broad  sense  of  transparent. 
2  Leitz  microscope.  No.  i  eye-piece  and  No.  7  objective. 


HYALINE  CASTS.  249 

segment  is  seen  with  both  ends  ragged.  Pure  hyaHne  casts 
are  free  from  granules,  and  are  therefore  often  very  difficult 
to  detect  in  the  sediment.  They  are  best  discovered  by 
reducing  the  amount  of  light  entering  the  microscope, 
either  by  manipulating  the  mirror,  or  by  interposing  the 
hand  between  the  source  of  light  and  the  mirror,  thus  shading 
the  microscopic  field.  As  a  rule,  the  casts  of  large  diameter 
are  somewhat  more  refracting,  and  thus  more  readily  de- 
tected than  the  small  narrow  casts. 

Not  infrequently  hyaline  casts  contain  a  few  very  fine 
granules  of  a  pale  color.  They  sometimes  exhibit  here  and 
there  upon  their  surfaces  a  renal  cell  or  a  blood  globule  or 
droplet  of  oil.     Such  casts  are  considered  strictly  of  the 


Fig.  40. — Pure  hyaline  casts. 


hyaline  order,  and  are  referred  to  as  hyaline  casts  with  a 
renal  cell  or  a  blood  globule  or  fat-drops  adherent,  as  the 
case  may  be. 

The  narrow  hyaline  casts  doubtless  have  their  origin  in 
the  smaller  undenuded  tubules,  while  those  of  large  diameter 
come  chiefly  from  the  large  straight,  or  collecting  tubules  of 
the  kidney.  In  advanced  disease  of  the  kidney,  notably 
chronic  interstitial  nephritis,  we  find  an  exception  to  the 
rule — /.  e.,  the  majority  of  the  casts  emanating  from  high  up 
in  the  kidney  are  of  large  diameter,  while  those  from  the 
collecting  tubules  are  very  large.  Such  casts  are  from  ex- 
tensively denuded  tubules,  the  result  of  the  advanced 
disease. 


250  URINARY  SEDIMENTS. 

Hyaline  casts  are  common  to  all  diseases  and  disturbances 
of  the  kidney,  and  not  pathognomonic  of  any  one  abnormal 
condition.  They  are,  however,  predominant  in  the  sedi- 
ment in  cases  of  chronic  interstitial,  chronic  diffuse  nephritis, 
amyloid  infiltration,  and  in  passive  hyperemia  ;  while  their 
relative  proportion  is  much  smaller  in  comparison  with  the 
other  forms  of  casts  present  in  active  hyperemia,  acute 
nephritis,  and  subacute  glomerular  nephritis. 

[2)  Fibrinous  Casts. — These  are  very  dense  or  JiigJdy 
refractive  casts,  usually  of  the  transparent  variety  and  ahuays 
of  a  yellozvish  color,  which  ranges  between  a  pale  yellow 
and  a  deep  brown.     (Plate  8.) 

Fibrinous  casts  are,  however,  sometimes  granular,  and 
often  have  renal  epithelial  cells  and  blood  globules,  and, 
not  infrequently,  oil-drops  adherent.  Like  the  pure  hya- 
line casts,  they  are  of  various  shapes  and  sizes,  but  being 
heavier  and  denser  than  the  hyaline  form,  show  a  greater 
tendency  to  crack  and  break,  thus  becoming  divided  into 
rather  short  segments,  the  ends  of  which  are  usually  thick 
and  ragged.  They  are  also  frequently  found  of  moderate 
length,  with  rounded  ends  ;  they  are,  as  a  rule,  of  larger 
diameter  than  the  average  hyaline  cast  found  in  the  sedi- 
ment. Fibrinous  casts  sometimes  have  so  little  color  as  to 
be  distinguished  with  difficulty  from  the  waxy  cast  that  is 
always  perfectly  colorless.  If  any  doubt  exists  in  the  mind 
of  the  observer  as  to  their  true  character,  the  term  "  highly 
refractive  casts  "  should  be  used,  until,  upon  further  study, 
the  observer  is  convinced  that  they  are  fibrinous  and  not 
waxy  casts.  The  bearing  of  this  suggestion  is  seen  in  the 
following  paragraph  : 

Fibrinous  casts  usually  accompany  blood  in  the  sedi- 
ment— in  other  words,  are  found  in  acute  diseases  or  dis- 
turbances of  the  kidney,  such  as  acute  nephritis,  and  some- 
times active  hyperemia ;  also  in  acute  exacerbations  of 
either  acute  or  chronic  renal  diseases.  The  fibrinous  cast 
is  simply  one  of  the  elements  of  an  acute  condition,  and  as 
this  condition  subsides,  it  disappears  from  the  sediment. 
Fibrinous  casts  do  not,  therefore,  indicate  an  unfavorable 
prognosis.  Waxy  casts,  on  the  other  hand,  are  practically 
unheard  of  in  active  hyperemia  and  acute  nephritis,  but  are 
most  often  found  in  the  sediment  in  the  advanced  forms  of 
kidney  disease,  their  presence  being  always  an  unfavorable 
prognostic  sign. 


Plate  8 


^^^12~i<^ 


P"i URINOUS  Casts. 


HYALINE  CASTS. 


251 


The  Xqxtcl  Jibri7io2is  as  applied  to  these  casts  is  inappro- 
priate, as  they  do  not  consist  of  fibrin,  nor  do  they  have 
any  relation  to  it,  only  resembling  fibrin  in  their  yellow  or 
brownish  color. 

(j)  Waxy  Casts. — These,  like  the  fibrinous  casts,  are 
very  higJdy  refractive  casts  of  the  transparent  variety,  and 
are  always  perfectly  colorless.  (Fig.  41.)  They  are  usu- 
ally of  large  diameter  and  often  very  long,  and  their  sur- 
faces may  be  marked  by  indentations  showing  imperfect 
vertical  segmentations  ;  they  often  have  a  serpentine  appear- 
ance. Not  infrequently,  waxy  casts  are  coarsely  granular, 
the  granules  apparently  having  the  same  composition  as 
the  cast  itself   (Fig.  41.)  They  may  have  fat-drops,  or  fatty 


Fig.  41. — Waxy  casts. 


renal  cells,  or  compound  granule  cells  adherent  to  them. 
On  account  of  their  thickness  and  density,  waxy  casts  are 
often  found  with  cracks  on  their  surfaces,  also  frequently 
found  in  segments,  with  one  or  both  ends  rough  and  irrep-- 
ular,  showmg  that  the  long  casts  have  become  broken  into 
several  small  pieces. 

Waxy  casts  should,  in  all  instances,  be  distinguished  from 
fibrinous  casts,  since,  as  has  already  been  explained,  they 
have  an  entirely  different  significance. 

Waxy  casts  are  found  in  the  sediment  in  the  advanced 
stages  of  all  chronic  diseases  of  the  kidney,  such  as  chronic 
interstitial,  chronic  diffuse,  and  subacute  (parenchymatous) 
nephritis,  and  are  of  bad  omen,  indicating  that  death  will 


252  URINARY  SEDIMENTS. 

probably  occur  within  a  comparatively  short  time,  usually  a 
year.  This  rule,  however,  is  not  invariable,  as  was  well 
demonstrated  by  a  case  that  the  author  observed  for  a 
period  of  over  two  years,  in  which  waxy  casts  were  con- 
stant, and,  as  was  shown  at  the  autopsy,  there  existed  a 
marked  chronic  diffuse  nephritis  of  the  parenchymatous 
variety.  Waxy  casts  are  a  frequent  accompaniment  of 
amyloid  infiltration  of  the  kidneys,  in  which  they  appear 
earlier  than  in  other  chronic  renal  diseases,  and  arc  of  de- 
cided diagnostic  value.  They  are  of  much  less  importance 
as  a  prognostic  sign  than  in  other  chronic  renal  affections. 

The  term  waxy,  as  applied  to  these  casts,  is  a  misnomer. 
It  was  formerly  supposed  that  waxy  casts  were  characteristic 
of  amyloid  infiltration  of  the  kidneys,  but,  as  has  been 
shown,  they  are  often  found  in  other  chronic  diseases  of  the 
kidney.  These  cacts  rarely  show  the  amyloid  reaction  with 
methyl-violet  and  with  iodopotassic-iodide  solution,  even 
when  amyloid  disease  of  the  kidneys  is  present. 

The  hyaline  cast  constitutes  the  basis  or  groundwork  of 
all  other  casts  to  be  described,  each  cast  being  named 
according  to  the  elements  adherent  to  or  embedded  in  it. 
Thus,  a  cast  covered  with  granules  is  called  a  granular  cast ; 
with  epithelium,  an  cpitliclial  cast ;  with  blood,  a  blood-cast, 
etc. 

II.  Granular  Casts. — These  casts  consist  of  a  hyaline 
basis  in  which  granules  are  embedded.  Various  terms  are 
applied  to  these  casts — i.  e.,  when  covered  with  fine  granules, 
finely  granular ;  with  coarse  granules,  coarsely  granular ; 
and  when  the  granules  are  colored  so  as  to  give  the  cast  a 
brown  color,  broivn  granular,  etc.     (Fig.  42.) 

The  granules  found  on  these  casts  probably  come  from 
the  renal  tubules,  and  are  the  result  of  the  degeneration  and 
disintegration  of  the  renal  epithelium.  At  times,  these 
granules  appear  to  result  partly  from  the  destruction  of 
blood-corpuscles  and  leucocytes.  This  is  particularly  the 
case  in  connection  with  the  brown  granular  casts,  which 
appear  to  derive  their  color  from  the  blood  pigment.  Bile 
naturally  stains  granular  casts  yellow  or  it  may  give  them  a 
brown  color.  Brown  granular  casts  nearly  always  accom- 
pany blood-casts. 

Granular  casts,  like  the  hyaline  forms,  have  a  variety  of 
shapes,  and  may  be  of  small,  medium,  or  large  diameter. 
They  are  usually  rather  short  and  have  rounded  ends  ;  not 


EPITHELIAL   CASTS. 


253 


infrequently,  however,  fragments  of  granular  casts  are  found 
with  rough  and  irregular  ends.  They  may  have  renal  epi- 
thelium, blood  globules,  fat,  or  leucocytes  adherent  to  their 
surfaces  or  embedded  in  them. 

Finely  granular  casts  are  found  in  ever}^  disease  or  dis- 
turbance of  the  kidney  ;  they,  therefore,  can  not  be  con- 
sidered pathognomonic  of  any  one  disease  or  class  of  dis- 
eases. 

III.  Epithelial  Casts. — These  are  casts  that  are  prac- 
tically covered  with  renal  epithelium.  (Fig.  43,  i.)  The 
renal  cells  may  be  embedded  in,  or  firmly  adherent  to, 
either  hyaline  or  granular  casts.  A  hyaline  cast  that  holds 
one,  two,  or  three  renal  cells   is  best  termed  a  hyaline  cast 


Fig.  42— a,  Hvaline  and  finely  granular  cast ;  b,  finely  granular  cast  ;<:,  coarsely 
granular  cast ;  d,  brown  granular  cast ;  e,  granular  cast  with  normal  and  abnormal 
blood  adherent ;  /,  granular  cast  with  renal  cells  adherent ;  g,  granular  cast  with  fat 
and  a  fatty  renal  cell  adherent. 


with  a  retial  cell  or  cells  adherent ;  the  same  applies  to  a 
granular  cast.  This  term  serves  to  distinguish  such  casts 
from  those  that  are  covered  with  renal  cells  and  properly 
called  epithelial  casts.  Renal  cells  on  casts  are  usually 
more  or  less  granular  and  swollen,  and  sometimes  they  are 
so  firmly  embedded  in  the  cast  that  their  outlines  are  ill 
defined.  The  nuclei  of  the  cells  often  stand  out  prominently, 
although  at  times  the  cells  are  so  granular  as  partially  or 
entirely  to  obscure  the  nuclei.  These  cells  may  also  con- 
tain fat  globules.  In  an  epithelial  cast  leucocytes  are 
frequently  found  mixed  with  the  epithelial  cells  ;  such  a 
cast,  which  consists  chiefly  of  epithelium,  should  not  be 
mistaken  for  a  true  pus-cast. 


254 


URINARY   SEDIMENTS. 


Epithelial  casts  are  most  commonly  found  in  those  path- 
ologic conditions  that  cause  an  exfoliation  of  the  renal 
epithelium,  such  as  severe  active  hyperemia,  acute  nephritis, 
and  subacute  glomerular  nephritis.  They  are  only  rarely 
found  in  the  urine  of  chronic  interstitial  nephritis  and  amy- 
loid infiltration  of  the  kidneys.  In  cases  of  extreme  renal 
irritation  and  congestion  the  epithelial  lining  of  the  tubules 
is  sometimes  thrown  off  intact  for  short  distances,  an  epi- 
thelial cylinder  possessing  a  lumen  resulting. 

IV.  Blood-casts. — These  are  of  two  kinds — i.e.,  {a)  a 
hyaline  or  granular  cast,  which  is  practically  covered  with 
blood  globules ;  and  (/;)  the  cylinder,  which  consists  of 
coagulated  blood — fibrin  with  blood  globules  firmly  em- 
bedded. 

Blood-casts   are  found  in  the  urine  in  those  conditions  in 


Fig.  43.— I,  Epithelial  cast;  2,  blood-cast;  3,  pus-cast;  4,  fatty  cast;  5,  fatty  cast 
with  a  compound  granule  and  fatty  renal  cell  adherent  (crystals  of  the  fatty  acids 
protruding). 


which  there  is  more  or  less  hemorrhage  into  the  renal 
tubules.  In  the  majority  of  instances  the  blood-cast  is 
made  up  of  abnormal  blood  (Fig.  43,  2),  in  which  case  the 
inference  is  that  either  the  blood  comes  from  high  up  in 
the  kidney  or  the  hemorrhage  into  the  tubules  is  very  slow. 
In  casts  of  this  kind  the  blood-corpuscles  are  unusually 
distinct,  but,  at  times,  indistinct,  requiring  careful  focus- 
ing in  order  to  make  out  the  faint,  deeply  embedded 
globules.  Not  infrequently  blood-casts  consist  of  nonnal 
blood  ;  under  such  circumstances  the  hemorrhage  is  usuall}' 
either  from  the  pyramidal  portion  of  the  kidney — straight 
tubules — or  is  very  abundant  and  from  higher  up  in  the 
kidney.  These  normal  blood-corpuscles,  which  still  have 
their  pale-yellow   color,    are    often    observed   agglutinated, 


FATTY  CASTS.  255 

at  times  forming  a  solid  mass  on  the  cast.  Ordinarily, 
however,  they  are  not  so  agglutinated  but  that  the  outlines 
of  the  individual  corpuscles  can  be  readily  seen.  Blood- 
casts  are  generally  short,  of  medium  diameter,  and  quite 
uniform  throughout,  usually  having  rounded  ends.  One 
portion  of  the  cast  may  be  hyaline  or  granular,  and  the  re- 
mainder covered  with  blood. 

Blood-casts  are  found  in  the  urine  in  hematuria  of  renal 
origin,  acute  diffuse  nephritis,  acute  renal  congestion,  and 
hemorrhagic  infarctions  of  the  kidneys.  Blood-casts  do  not 
in  themselves  furnish  positive  evidence  of  organic  renal  dis- 
ease, since  any  hemorrhage  from  the  kidney  may  be  asso- 
ciated with  blood-casts  in  the  urine.  On  the  other  hand,  it 
may  be  stated  that  the  presence  of  blood-casts  constitutes  the 
only  positive  evidence  of  the  existence  of  renal  hemorrhage. 

V.  Fatty  Casts. — These  are  casts  that  are  thickly 
studded  with  fat  drops.  (Fig.  43,  4.)  It  has  already  been 
stated  that  a  hyaline  or  granular  cast  may  have  oil  globules 
attached,  but  the  term  fatty  cast  only  applies  to  those  that 
are  practically  covered  with  fat.  At  times,  fine  needle-  or 
hair-like  crystals  of  the  fatty  acids  are  found  protruding 
from  these  casts,  and  they  may  have  fatty  renal  cells  and  com- 
pound granule  cells  embedded  in  or  attached  to  them.  (Fig. 
43 »  5-)  Generally,  the  fat-drops  are  small  and  appear  as 
glistening  points  ;  such  should  not  be  mistaken  for  the  less 
highly  refracting  granules  not  fat.  Sometimes  the  globules 
are  large,  when  they  are  easily  recognized.  Fatty  casts  indi- 
cate that  a  fatty  degeneration  of  the  kidney  is  in  progress, 
since  the  fat  is  probably  the  result  of  extreme  degeneration 
of  the  renal  cell  protoplasm.  They  are  not  necessarily  in- 
dicative of  a  chronic  kidney  disease,  although  most  common 
in ,  subacute  glomerular  (chronic  parenchymatous)  and 
chronic  diffuse  nephritis.  They  are  also  found  during  the 
fatty  stage  of  an  acute  nephritis,  and  occasionally  in  severe 
renal  congestion. 

VI.  Pus-casts. — Pus-casts  are  tho.se  that  are  covered 
with  pus-corpuscles  or  leucocytes.  (Fig.  43,  3.)  The  cor- 
puscles are  generally  highly  granular,  and  often  so  much  so 
that  their  nuclei  are  entirely  obscured.  Under  such  cir- 
cumstances, because  of  failure  to  make  out  the  nuclei,  casts 
that  are  covered  with  pus-corpuscles  are  often  considered 
to  be  epithelial  casts.  Such  inference  should  not  be  drawn 
without  first  thoroughly  treating  the  sediment  with  dilute 


256  URINARY   SEDIMENTS. 

acetic  acid,  which  dissolves  the  granular  matter,  thus  caus- 
ing the  nuclei  of  the  leucocytes  and  the  nucleus  of  the 
cell  to  stand  out  prominently. 

Hyaline  or  granular  casts  with  one,  two,  or  three  leuco- 
cytes adherent  are  frequently  found  in  acute  diseases  and 
disturbances  ;  also  in  acute  exacerbations  occurring  during 
the  course  of  a  chronic  disease  of  the  kidneys.  True  pus- 
casts,  on  the  other  hand,  are  quite  uncommon,  and,  when 
present,  indicate  a  chronic  suppurative  process  in  some 
portion  of  the  kidney.  Pus-casts  may  be  formed  in  case 
there  is  an  abscess  of  the  kidney  or  tuberculosis  of  this 
organ  ;  also  in  cases  of  chronic  pyelitis  with  extension  into 
the  straight  tubules,  in  which  instance  they  are  usually  of 
large  diameter. 

Bacterial  Casts. — True  casts  when  covered  with  bacteria 
have  received  the  name  "  bacterial  casts."  Accidental 
aggregations  of  bacteria  that  closely  resemble  renal  casts  in 
shape  and  size,  and  seen  particularly  in  urines  that  have 
been  exposed  to  the  air  for  a  long  time,  should  not  be  mis- 
taken for  bacterial  casts.  True  bacterial  casts  closely 
resemble  the  brown  granular  casts,  and  are  distinguished 
from  the  latter  by  their  resistance  to  certain  chemicals,  such 
as  acetic  acid,  mineral  acids,  and  strong  alkalies.  It  is 
almost  impossible  to  distinguish  between  them  by  means  of 
the  microscope,  particularly  if  the  bacteria  belong  to  the 
class  of  micrococci  as  is  usually  the  case.  Bacterial  casts 
are  very  uncommon,  and  are  chiefly  found  in  the  septic 
forms  of  renal  disease,  especially  those  accompanied  by 
embolism,  and  are  therefore  a  grave  prognostic  sign.  They 
are  sometimes  found  in  the  ascending  form  of  chronic  pyelo- 
nephritis or  "surgical  kidney." 

VII.  Crystalline  Casts. — These  are  of  three  kinds,  and 
are  named  according  to  the  form  of  crystal  adherent  to  or 
embedded  in  them.  Thus,  a  urate  cast  is  one  that  is 
covered  with  crystals  of  ammonium  urate,  usually  the 
hedgehog  crystals  ;  the  cystin  cast,  covered  with  hexagonal 
crystals  of  cystin,  as  seen  rarely  in  cases  of  cystinuria ;  and 
the  calcimn  oxalate  cast,  covered  with  the  octahedral,  oval, 
or  dumb-bell  crj^stals  of  calcium  oxalate.  As  a  rule, 
cr}'stalline  casts  show  that  the  cr}^stals  deposited  thereon 
were  separated  in  the  kidney,  and  therefore  primary.  Occa- 
sionally, crystals  are  deposited  on  casts  secondarily — that 
is,  after  the  urine  has  been  voided. 


FALSE   CASTS.  257 

False  Casts. — False  casts,  also  termed  mucin  casts, 
shreds,  or  cyllndroids,  are  not  infrequently  found  in  the  sedi- 
ment. They  are  long,  flat  structures,  usually  with  fine, 
wavy,  longitudinal  striations,  and  long  tapering  ends.  (Fig. 
44.)  They  are  colorless,  often  twisted  or  folded,  and 
usually  free  from  adherent  elements,  although  they  may 
have  cells,  leucocytes,  and  blood  globules  adherent.  False 
casts  are  usually  longer  than  the  true  renal  casts  just 
described,  and  appear  to  be  flat  and  not  cylindric.  It  is 
probable  that  these  structures  consist  only  of  coagulated 
nucleo-albumin  or  mucin,  although  the  subject  requires 
further  investigation  in  order  to  determine  their  true  nature. 
It  is  sufficient  to  say  that  they  are,  apparently,  not  true 
casts,  that  they  are  frequently  present  in  a  urine  that  is  free 
from  albumin,  and  that  they  are  of  little  clinical  importance. 

False  casts  may  originate  in  the  kidney,  but  they  are 
most  commonly  found  in  the  sediment  in  connection  with 


Fig-  44-— False  casts  or  cylindroids  (after  von  Jaksch). 

irritation  or  inflammation  of  the  lower  urinary  passages, 
particularly  of  the  bladder,  prostatic  region,  and  urethra. 
They  may  be  found  in  the  prostatic  ducts  as  a  result  of  mild 
or  severe  inflammatory  processes,  when  they  are  usually 
accompanied  by  a  large  number  of  mucin  (nucleo-albumin) 
threads  or  shreds.  It  is  often  exceedingly  difficult  to  dis- 
tinguish these  so-called  prostatic  casts  from  true  renal  casts  ; 
in  fact,  these  two  structures  may  exist  in  the  same  urinary 
sediment. 

Prostatic  Plugs. — These  bodies,  occasionally  found  in 
the  urinary  sediment,  are  evidently  formed  in  the  prostatic 
ducts.  They  appear  to  be  cylindric,  often  with  rounded 
ends,  and  are  usually  of  large  diameter,  but  may  be  of 
irregular  shape,  as  from  a  dilated  duct  or  cavity.  They  are 
either  colorless  or  colored  yellow,  when  they  have  much 
the  appearance  of  fibrinous  casts.  Prostatic  plugs  usually 
have  spermatozoa  embedded  in  them,  and,  at  times,  leuco- 
17 


258 


URINARY  SEDIMENTS. 


cytes  or  epithelial  cells  from  the  prostatic  ducts  are  firmly- 
adherent  to  them. 

These  bodies  are  found  most  commonly  in  mild  inflam- 
matory processes  that  involve  the  region  of  the  neck  of  the 
bladder  and  the  prostatic  ducts. 

Spermatozoa. — Spermatozoa  are  frequently  found  in  the 
urine  of  healthy  men.  They  are  bodies  about  50  //  in 
length,  and  consist  of  an  oval  head,  or  body,  about  4.5  // 
in  length,  to  which  is  attached  a  long,  tapering  whip-like 
tail  of  extreme  delicacy.  (Fig.  45.)  When  freshly  ejected, 
they  exhibit  active  eel-like  movements,  strongly  suggestive 


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Fig.  45. — Spermatozoa. 


of  volition ;  but  as  seen  in  the  urine  they  are  always 
motionless.  The  cause  of  the  movements  in  spermatozoa 
is  unknown,  although  Roberts  claims  that  they  are  floating 
cilia  and  resemble  the  oscillating  sperm-cells  of  the  anther- 
idae  of  mosses.  Their  movements  are  arrested  by  water, 
alcohol,  ether,  drying,  etc.  They  resist  putrefaction,  and 
when  once  dried,  may,  after  years,  be  restored  to  their 
original  form  by  moistening  them  with  a  weak  solution  of 
sodium  chloride  or  potassium  acetate.  Spermatozoa  are 
usually  accompanied  by  medium-sized,  highly  granular 
cells  ;  also  by  finely  granular  cells  with  one  or  more  nuclei ; 
more  rarely,  by  lecithin  corpuscles  and  spermatic  crystals. 


CORPORA  AMYLACE/E.  259 

Clinical  Significance. — A  certain  number  of  spermatozoa 
necessarily  find  their  way  into  the  urine  of  both  sexes  after 
coitus  ;  also  into  the  urine  of  men  after  involuntary  nocturnal 
emissions.  The  persistent  absence  of  spermatozoa  from 
the  seminal  fluid  indicates  sterility.  The  recognition  of 
spermatozoa  is  most  important  in  connection  with  medico- 
legal cases — cases  of  suspected  rape.  Their  presence  in 
vaginal  secretion  soon  after  coition  and  in  stains  upon  linen 
is  easy  of  demonstration.  Spermatozoa  are  sometimes 
found  in  the  urine  in  cases  of  severe  acute  febrile  disease, 
such  as  typhoid  fever,  pneumonia,  and  acute  septic  condi- 
tions, also  following  convulsions.  They  are  of  frequent 
occurrence  in  cases  of  acute  or  chronic  prostatitis  or  irrita- 
tion in  the  prostatic  region.  The  condition  of  spermator- 
rhea is  characterized  by  the  constant  presence  of  sperma- 
tozoa. 

Detection. — Spermatozoa  are  best  detected  by  their  char- 
acteristic appearance  under  the  microscope.  Florence,^  of 
Lyons,  has  recently  described  a  characteristic  reaction  that 
takes  place  between  iodine-potassium  iodide  and  seminal 
fluid. 

Florence  Reaction. — The  reagent  is  prepared  as  follows  : 

Potassium  iodide, 1.65  giams. 

Iodine,      2.54     " 

Distilled  water, 30  " 

The  iodine-potassium  iodide  in  this  mixture  corresponds  to 
the  formula  KI3. 

A  small  portion  of  the  suspected  seminal  fluid  is  treated 
with  a  drop  of  the  foregoing  reagent.  If  semen  be  present, 
small,  dark,  rhombic  crystals  appear,  which  are  very  simi- 
lar in  their  general  appearance  to  the  hemin  crystals  ob- 
tained in  Teichmann's  test  for  blood.  So  far  as  is  known, 
no  other  secretion  of  the  body  gives  this  reaction. 

Corpora  Amylaceae. — The  so-called  amyloid  bodies,  or 
corpora  amylaceae,  have  somewhat  the  appearance  of  starch 
granules,  but  they  differ  from  starch  in  their  chemic  re- 
actions. They  are  microscopic,  spheroid,  homogeneous, 
or  lamellated  bodies  (Fig.  46),  usually  containing  within 
them  a  core,  which  is  also  frequently  lamellated  and  some- 
times colored.      They  do   not  swell   when   soaked   in    hot 

1  Florence,  "  Du  Sperme  et  des  Taches  de  Sperme  en  Medecine  Legale," 
1897. 


260  URINARY  SEDIMENTS. 

water,  and  are  not  split  up  by  boiling  with  dilute  mineral 
acids  ;  they  are  not  dissolved  by  fuming  nitric  acid.  Amy- 
loid bodies  are  colored  red  by  methyl-violet,  while  starch 
is  colored  blue.  When  the  former  are  treated  with  iodine 
or  iodine-potassium-iodide  solution,  they  not  infrequently 
show  a  violet  to  a  blue  color,  which  becomes  distinctly 
blue  by  the  subsequent  action  of  sulphuric  acid.  These 
bodies  seem  to  have  no  connection  with  amyloid  infil- 
tration, although  they  sometimes  resemble  its  products. 
They  may  occur  normally  as  well  as  under  pathologic  con- 
ditions, and  are  apparently  of  little  clinical  importance. 

Corpora  amylacese  are  frequently  found  in  the  acini  of 
the  prostate  gland,  from  which  they  may  find  their  way 
into  the  urine,  sometimes  in  large  numbers.  They  are  also 
found  in  the  ependyma  of  the  ventricles  of  the  brain  and  in 


Fig.  46.— Corpora  amylaceae. 

areas  of  sclerosis  of  the  brain  and  cord  ;  also  in  extravasa- 
tions of  blood  in  various  other  situations.  The  amyloid 
bodies  represented  in  figure  46  were  found  by  the  author  in 
the  urine  of  a  man  who,  several  days  before,  had  had  an 
extensive  hemorrhage  from  the  prostatic  region.  At  the 
time  these  bodies  were  found  the  urine  was,  however,  free 
from  blood.  In  the  experience  of  the  writer  these  so-called 
amyloid  bodies  are  a  rare  constituent  of  the  urinaiy  sedi- 
ment. 

Amyloid  Concretions. — These  are  frequently  found  in 
the  prostate  gland  of  old  people.  They  are  sometimes 
large  enough  to  be  detected  with  the  naked  eye,  and  are 
usually  hard,  and  often  have  a  dark  color  due  to  the  depo- 
sition of  pigment.     (See  Prostatic  Concretions,  p.  280.) 


EXTRANEOUS  SUBSTANCES.  261 


EXTRANEOUS  SUBSTANCES  FOUND  IN  URINE. 

These  are  very  numerous,  and  include,  indeed,  all  sub- 
stances that  are  liable  to  get  into  vessels  containing  the 
urine.  The  most  common  of  these  are  fibers  of  cotton  and 
linen,  hair  of  blankets,  worsted,  wool,  human  hair,  cats' 
hair,  splinters  of  wood,  oil  globules,  starch  granules,  lyco- 
podium  and  other  pollen,  tea  leaves,  bread  crumbs,  particles 
of  glass,  dust,  etc.  It  is  a  common  custom  with  some 
persons  to  expectorate  into  the  vessel  that  is  to  contain 
the  urine  or  into  the  urine  after  it  has  been  voided,  hence 
pavement  epithelium  containing  pigment  granules,  particles 
of  food,  free  oil,  etc.,  will  be  found.  It  is  very  important 
that  the  student  should  become  familiar  with  the  microscopic 
appearances  of  all  these  extraneous  elements  before  he  be- 
gins the  examination  of  urinary  sediments. 


PRESERVATION  OF  URINARY  SEDIMENTS. 

In  order  to  preserve  urinary  sediments  it  is  necessary  to 
treat  the  urine  and  its  sediment  in  such  a  way  as  to  prevent 
subsequent  changes,  of  which  the  most  common  are  ammon- 
iacal  decomposition  and  the  formation  of  vegetable  growths. 
To  accomplish  this  end,  the  coloring-matters  and  the  salts 
of  the  urine  must  be  remov^ed  by  washing  with  those  media 
that  will  take  up  the  soluble  urinary  constituents  and,  at  the 
same  time,  leave  the  sediment — cells,  casts,  crystals,  etc. — 
in  the  same  condition  as  found  in  the  fresh  urine. 

Epitliclial  cells,  renal  casts,  blood,  pus,  fat,  and  fibrin, 
are  best  preserved  in  the  following  manner :  Allow  the 
urine  to  settle  thoroughly  in  a  urine  glass,  or  centrifugalize, 
and  wash  by  decantation  twice  with  a  saturated  aqueous 
solution  (4  per  cent.)  of  boric  acid,  and  then  three  times 
with  an  aqueous  solution  of  potassium  acetate  (specific 
gravity,  1030)  containing  y^  of  i  per  cent,  of  formalin. 
The  sediment  is  left  in  the  last  washing  of  potassium  acetate 
and  formalin,  and  is  then  placed  in  a  tightly  stoppered  bottle, 
where  it  will  keep  for  months  and  years.  By  this  process 
the  sediment  suffers  very  little,  if  any,  change,  excepting 
that  any  blood  that  was  originally  in  the  sediment  as 
normal  blood  will  be  changed  to  abnormal  blood. 

Crystalline  sediments  on  account  of  their  solubility  in  the 
media  already  given   require  different   treatment,  the  pre- 


262  URINARY  SEDIMENTS. 

servative  used  varying  with  the  form  of  crystal  to  be  pre- 
served. 

Uric  acid,  calcium  oxalate,  hippuric  acid,  cystin,  and 
cholcsicrin  crystals  should  be  washed,  by  decantation,  several 
times  with  a  small  volume  of  very  dilute  acetic  acid  (i  to  2 
per  cent.),  and,  finally,  after  all  of  the  soluble  urinary  salts 
have  been  removed,  left  in  the  last  washing.  This  is  then 
placed  in  a  perfectly  clean,  tightly  stoppered  bottle. 

Acid  amjnonitim  urate  and  acid  sodium  urate  crystals 
should  be  washed,  by  decantation,  several  times  with  a  small 
volume  of  33  per  cent,  alcohol,  and,  after  all  of  the  soluble 
urinary  salts  have  been  removed,  left  in  the  last  washing, 
and  then  placed  in  a  clean,  tightly  stoppered  bottle. 

Triple  phosphate  and  acid  calcium  phospJiatc  crystals  should 
be  washed,  by  decantation,  several  times  with  a  small  wo\\xvc\q 
of  very  dilute  ammonic  hydrate  (i  to  2  per  cent.),  finally 
left  in  the  last  washing,  and  placed  in  a  clean,  well-stoppered 
bottle. 

Some  of  these  crystals,  such  as  the  oval  and  dumb-bell 
forms  of  calcium  oxalate,  cystin,  triple  phosphate,  and  acid 
calcium  phosphate,  frequently  undergo  partial  solution  in 
their  respective  media,  particularly  when  kept  in  the  bottle 
for  several  months  or  years.  All  crystalline  sediments  keep 
better  when  mounted  on  glass  slides  ;  it  is,  therefore,  advis- 
able to  mount  them  as  soon  as  possible  after  washing. 

The  washing  can  be  done  by  the  centrifugal  or  the 
gravity  methods,  the  former  having  the  advantage  of  com- 
pleting the  washing  in  a  few  hours  and  before  bacteria  or 
other  foreign  substances  enter  the  fluid. 

The  Mounting  of  Urinary  Sediments. — After  the  sedi- 
ments have  been  prepared  in  the  manner  described  they 
can  be  mounted  on  glass  slides,  and  thus  preserv^ed  for 
years. 

Method. — Place  a  glass  slide  on  a  turn-table  and  make  a 
cell  by  the  use  of  Bell's  cement  and  a  camel's-hair  brush. 
Allow  the  cement  to  dry  thoroughly.  Place  a  drop  of  the 
prepared  sediment  within  the  cell,  and  cover  with  a  circular 
cover-glass  of  such  a  size  that  its  margin  rests  well  on  the 
ring  of  cement.  Take  up  the  excess  of  fluid  from  around 
the  cover-glass  by  means  of  a  piece  of  filter-paper,  care  being 
taken  not  to  admit  air  to  the  cell,  and  also  to  remove  all  air- 
bubbles  that  may  be  present.  Return  the  slide  to  the  turn- 
table, and  carefully  cover  the  margin  of  the  cover  with  Bell's 


MICRO-ORGANISMS.  263 

cement  so  as  to  make  the  cell  air-tight.  Allow  this  layer  of 
cement  to  dry,  and  in  two  or  three  days  apply  another  coat. 
Mounts  prepared  in  this  manner  will  in  most  instances  keep 
several  years,  and  are  very  useful  for  purposes  of  demon- 
stration or  for  reference. 

MICRaORGANISMS. 

The  micro-organisms  that  are  found  in  the  urine  belong  to 
the  following  different  classes  :  Bacteria  (nonpathogenic  and 
pathogenic),'  molds,  and  yeasts,  all  of  which  properly  belong 
to  one  general  class  called  f2iiigi. 

Fresh  normal  urine  is  free  from  bacteria  or  other  micro- 
organisms, and,  as  has  been  repeatedly  demonstrated,  is  a 
sterile  fluid.  Numerous  investigations  have  shown  that 
bacteria  are  usually,  if  not  always,  present  in  the  urethra  of 
both  the  male  and  female,  particularly  near  the  meatus  ; 
therefore  urine  that  was  sterile  intra  vesicam  becomes  con- 
taminated as  it  passes  through  the  urethra. 

Bacteria,  being  vegetable  in  their  nature,  belong  to  the 
class  of  fungi,  and  for  purposes  of  study  are  more  conven- 
iently divided  into  two  classes  :  {a)  nonpathogenic  or  those 
that  are  innocuous,  and  {b)  pathogenic  forms  or  those  that 
are  pyogenic  in  their  nature. 

(a)  Nonpathogenic  Forms. — As  already  stated,  fresh 
normal  urine  is  free  from  bacteria,  but  when  such  urine  is 
allowed  to  stand  exposed  to  the  air  for  some  time,  it  soon 
becomes  crowded  with  micro-organisms  of  various  kinds, 
rendering  the  urine  turbid  and,  for  the  most  part,  unfit  for  a 
satisfactory  examination. 

The  microscopic  appearance  of  fermenting  normal  urine 
is'  subject  to  much  variation.  The  conversion  of  urea  into 
ammonium  carbonate  is  probably  effected  through  the 
agency  of  several  forms  of  micro-organisms  (Leube,  C. 
Fliigge,  v.  Jaksch,  v.  Limbeck),  of  which  the  micrococcus 
iirece  (Fig.  47)  is  the  most  prominent,  and  at  times  may  be 
seen  in  almost  pure  culture  upon  the  surface  of  the  decom- 
posing fluid.  These  micrococci  form  in  long  chain-like 
series,  although  they  may  occur  as  free,  round,  highly  re- 
fracting dots  ;  they  are  usually  of  comparatively  large  size, 
and  are  constant  inhabitants  of  the  air.  Of  the  other  micro- 
organisms that  have  a  part  in  the  decomposition  of  urea,  the 
staphylococcus  urecB  candidus  and  staphylococcus  Jirece  lique- 


264 


URINARY   SEDIMENTS. 


facials  (Lundstrom),  bacillus  iirccc  (Leube),  iirobacilhis 
Frciidcnrcichii,  and  the  urobacillits  Maddoxii  should  also  be 
mentioned.  It  is  claimed  that  the  urobacillus  Maddoxii  is 
the  micro-organism  that  renders  the  urine  viscid  and 
stringy.  A  number  of  other  bacteria  have  been  isolated 
from  decomposing  urine,  but  little  is  yet  known  of  their 
importance.     Occasionally,  long    spiral    bacilli    with  large 


Fig.  47. — Micrococcus  ureae  (after  v.  Jaksch). 

spores,  and  cocci  that  group  themselves  in  globular  masses 
of  varying  sizes  are  met  with  in  the  urine. 

Molds  are,  under  normal  circumstances,  a  very  rare  mani- 
festation in  decomposing  urine.  In  diabetic  urine,  however, 
they  not  infrequently  make  their  appearance,  especially  after 
the  alcoholic  fermentation  has  ceased.  They  are  then  found 
floating  in  a  layer  on  the  surface  of  the  urine.  The  urine 
is  at  the  same  time  more  or  less  turbid  with  bacteria  and 
yeast  fungi. 


Fig.  48. — Sediment  from  fermenting  diabetic  urine  with  casts  of  micrococci : 
a,  b,  c.  Various  forms  of  uric  acid  ;  d,  micrococci  in  form  of  casts ;  e,  molds  ;  jT,  yeast 
fungi ;  g,  bacilli  and  micrococci  (after  v.  Jaksch). 


The  yeast  fungus  of  the  urine  (saccharomyces  urinae) 
consists,  in  the  sporule  stage,  of  transparent  oval  cells,  which 
are  seen  both  singly  and  in  rows  of  two,  three,  or  more. 
(Fig.  48,  f.)  They  are  found  in  saccharine  urine,  and  are 
identical  with  the  yeast  fungus  (saccharomyces  cerevisiae). 
They  grow  in  acid  urine,  but  cease  to  multiply  as  soon  as 
the  urine  becomes  alkaline. 


MICRO-ORGANISMS.  265 

Yeast  spores  are  distinguished  from  normal  blood-corpiis- 
clcs  by  the  fact  that  the  former  are  smaller,  perfectly  color- 
less, and  have  usually  a  focal  point.  They  differ  from 
abnormal  blood-corpuscles  in  having  an  oval  shape,  a  focal 
point  seen  especially  in  the  larger  sporules,  and  a  cell-body, 
the  abnormal  blood  globule  appearing  simply  as  a  ring 
— that  is,   apparently   without  a  cell-body.     (Compare  p. 

231-) 

The  presence  of  the  yeast  fungus  in  the  urine  is  always 
suggestive  of  the  presence  of  sugar,  but  in  the  experience 
of  the  writer  this  rule  is  by  no  means  invariable.  It  occa- 
sionally happens  that  the  urine  to  be  examined  is  placed  in 
a  bottle  containing  a  mere  trace  of  syrup  ;  in  such  a  urine 
the  yeast  fungus  grows  rapidly. 

Penicilli2im glaucnm  is  not  infrequently  met  with  in  acid 
urine  with  or  without  sugar  or  albumin.  The  sporule  stage 
furnishes  cells  very  similar  to  those  of  the  yeast  fungus, 
but  later  the  penicillium  multiplies  by  linear  division  of 
cells,  forming  threads  that  have  a  characteristic  appearance. 

The  sarcina  nrince  is  a  fungus  only  occasionally  seen  in 
the  urine.  It  is  smaller  than  that  which  forms  in  the 
stomach  (sarcina  ventriculi),  being  in  point  of  size  compar- 
able to  the  sarcina  of  the  lung.  They  are  cubes,  each 
group  of  eight  cells  being  so  arranged  as  to  resemble  a 
"  bale  of  goods." 

(b)  Pathogenic  Forms. — The  pathogenic  micro-organ- 
isms found  in  the  urine  may  be  divided  into  two  classes — 
i.  e.,  micrococci  and  bacilli.  Of  the  micrococci  the  strepto- 
coccus pyogenes,  the  staphylococcus  pyogenes  albus,  citrcus, 
and  aureus,  and  the  gonococcus  of  Neisser  are  the  most  im- 
portant. The  most  common  bacilli  found  in  the  urine  are 
the  bacillus  coli  communis,  the  urobacillus  liquefaciens  scpti- 
cus,  and  the  tubercle  bacillus. 

When  recently  voided  urine  is  found  to  contain  patho- 
genic micro-organisms,  the  condition  becomes  serious  on 
account  of  the  marked  tendency  to  decomposition  of  the 
urine  within  the  bladder.  These  micro-organisms  occur  in 
the  freshly  voided  urine  in  connection  with  certain  specific 
diseases,  such  as  typhoid  fever,  erysipelas,  relapsing  fever, 
ulcerative  endocarditis,  glanders,  malignant  pustule  (bacillus 
of  anthrax),  septic  processes,  and  tuberculosis.  The  spirilla 
of  relapsing  fever  occur  very  rarely  and  only  when  hemor- 
rhage takes  place  in  the  kidney  during  an  exacerbation  (v. 


266  URINARY  SEDIMENTS. 

Jaksch).  According  to  Horton-Smith,i  the  freshly  voided 
urine  of  typhoid  fever  is  usually  turbid  from  the  presence 
of  the  typhoid  bacilli.  Richardson  ^  has  recently  shown 
that  the  virulence  of  these  bacilli  is  destroyed  by  the  inges- 
tion of  urotropin  (a  formaldehyde  compound).  Actinomyces 
may  also  occur  in  the  urine  in  instances  in  which  the  genito- 
urinary tract  is  infested  with  it,  or  in  those  cases  in  which 
it  enters  this  tract  from  other  parts  (Braatz).  Lustgar- 
ten  and  Mannaberg  have  found  cocci  in  the  urine  in  acute 
nephritis  ;  and  Letzerich  has  found  bacilli  in  the  "  primary 
nephritis  "  of  children.  Mircoli  also  determined  the  pres- 
ence of  pneumococci-like  forms  in  the  urine  of  children 
suffering  from  acute  nephritis.  Schweiger  has  demonstrated 
that  in  scarlet  fever  the  urine  is  distinctly  contagious;  and 
he  claims  that  all  renal  lesions  arising  in  the  course  of  in- 
fectious fevers  are  caused  by  micro-organisms. 

In  recent  years  the  recognition  of  the  tubercle  bacillus  in 
the  urine  or  urinary  sediment  has  been  attended  with  great 
pathologic  interest.  A  detailed  consideration  of  this  sub- 
ject, together  with  the  method  best  adapted  to  the  detec- 
tion of  tubercle  bacilli,  will  be  found  on  page  323.  It  is  of 
great  importance  to  differentiate  the  tubercle  bacillus  from 
the  smegma  bacillus,  which  is  frequently  present  in  the  urine. 

Gonococci  consist  of  diminutive  kidney-shaped  cocci 
aggregated  in  large  groups.  They  are,  for  the  most  part, 
diplococci  with  the  flattened  surfaces  of  the  kidney-shaped 
cocci  presenting  to  each  other.  They  are  often  found  in 
abundance  in  the  gonorrheal  discharge  from  the  urethra, 
within  the  pus-corpuscles  and  exfoliated  epithelial  cells,  as 
well  as  free  in  the  shreds  of  mucin.  It  has  been  satisfac- 
torily demonstrated  that  diplococci,  in  all  respects  resem- 
bling gonococci,  exist  in  the  genital  tract.  It  is,  therefore, 
exceedingly  important  from  a  diagnostic  point  of  view  to 
distinguish  the  gonococci  from  those  that  closely  resem- 
ble them.  This  is  best  accomplished  in  the  following  way  : 
First,  stain  a  preparation  with  Loeffler's  solution  of  methyl- 
ene-blue.  If  the  characteristic  groups  of  diplococci  are 
found  in  the  cells  and  pus-corpuscles,  then  stain  a  new 
preparation  by  Grain's  method,  as  follows  :  (i)  Cover  the 
preparation    with    aniline-gentian-violet    solution    (without 

^  "Transactions  of  the  Medical  and  Surgical  Society,"  London. 
*"  The  Journal  of  Experimental   Medicine,"  vol.  iv,  No.  I,  1899. 


PARASITES.  267 

heat)  for  thirty  seconds  ;  (2)  wash  in  water  for  two  or  three 
seconds ;  (3)  cover  the  preparation  with  Gram's  solution 
of  iodine  (iodine,  i  part ;  potassium  iodide,  2  parts  ;  water, 
250  parts)  for  thirty  seconds  ;  (4)  wash  with  95  per  cent, 
alcohol  until  the  color  ceases  to  come  out  of  the  prepara- 
tion ;  (5)  wash  in  water  for  two  or  three  seconds  ;  (6) 
counterstain  with  saturated  aqueous  solution  of  Bismarck 
brown  ten  seconds  ;  (7)  wash  in  water,  mount,  and  examine. 
Gonococci  are  stained  brown,  while  other  diplococci  are 
stained  blue  by  this  method. 

PARASITES. 

Filaria  Sanguinis  Honiinis. — This    is    the    parasite  that 
causes  the  condition  of  chyluria.     This  parasite  was  first  dis- 


Fig.  49. — Eggs  of  distoma  hsematobimn  in  sediment  (after  v.  Jaksch). 

covered  and  described  by  Lewis,  of  Calcutta,  who  found 
them  in  large  numbers  in  the  urine  and  blood  of  persons 
who  were  passing  milk)-  or  chylous  urine. ^ 

Distoma  Hcematobinni. — The  eggs  of  this  parasite  are 
often  found  both  in  the  urinary  passages  and  in  the  urine 
of  inhabitants  of  tropical  climates.  This  worm  infests  the 
north  and  east  coasts  of  Africa,  and,  according  to  Brock,  is 
found  also  in  South  Africa.  The  eggs  are  oval,  slender 
bodies,  about  o.  1 2  mm.  long  and  0.04  mm.  broad,  and  fur- 
nished  with   a   small    spike,  which   projects   from   the  ex- 

1  A  detailed  account  of  this  parasite,  together  with  an  illustration  of  the 
same,  will  be  found  under  the  subject  of  Chyluria,  p.  360. 


268 


URINARY   SEDIMENTS. 


tremity  or  from  the  side.  (Fig.  49.)  Both  the  male  and 
female  parasites  have  been  found  in  the  branches  of  the 
portal  vein,  the  splenic  vein,  the  vesical  plexus,  etc.,  and 
are  nourished  by  the  blood.  The  male  is  from  1 2  to  14  mm. 
long,  and  the  female  is  from  16  to  20  mm.,  and  nearly 
cylindric  in  shape.  (Fig.  50.)  In  case  the  individual  is 
infested  with  this  parasite  the  most  prominent  symptom  is 


Fig.  50. — Distoma  haematobium  ;  male  and  female,  with  eggs  (after  v.  Jaksch). 

severe  burning  pain  during  micturition.  The  pain  is  usu- 
ally momentary,  and  caused  by  the  passage  of  the  eggs 
along  the  urethra,  which  they  irritate  by  their  sharp  angles. 
The  urine  usually  contains  blood-  and  pus-corpuscles,  with 
eggs  of  the  parasite,  and  sometimes  a  considerable  quantity 
of  fat.  There  are  often  marked  cystitis,  pyelitis,  sometimes 
nephritis,  and  septic  processes. 

Echinococci. — Echinococcus    cysts    have   been   found    in 


'^ 
^ 


Fig.  51.— Echinococcus  scolices  and  hooklets  (after  Heller). 


the  kidney,  although  rarely.  Usually,  only  one  kidney  is 
affected.  The  hydatid  growth  is  made  up  of  an  outer  cap- 
sule, within  which  the  mother  cysts  are  found.  Within 
the  mother  cysts  are  the  daughter  cysts.  Both  the  large 
mother  cysts  and  the  smaller  daughter  cysts  float  freely  in 
the  liquid  contents  of  the  capsules  holding  them.  This 
peculiar  growth  is  caused  by  a  very  small  tapeworm, — the 


PARASITES. 


269 


tcenia  cchinococciis, — whose  natural  size  is  about  that  of  a 
millet  seed,  (Fig.  52.)  This  worm  consists  of  a  head 
much  like  that  of  the  ordinary  tapeworm,  four  mouths  or 
suckers,  and  a  double  row  of  booklets. 

The  scolices  and  booklets  (Fig.  5  i)  occasionally  find  their 
way  into  the  urine,  either  from  the  cysts  in  the  kidney  or 
from  some  neighboring  organ,  as  the  result  of  rupture.     The 
booklets    are    usually   accompanied    by 
more  or  less  blood,  leucocytes,  and  at 
times  shreds  of  membrane  forming  the 
hydatid  cyst.      The  diagnosis  of  echino- 
coccus    growth   of   the   kidney   is    only 
made  with  certainty  by  finding  charac- 
teristic booklets  in  the  urinary  sediment. 

Hydatid  disease  of  the  kidney  in  man 
is  most  commonly  contracted  from  the 
dog,  whose  intestinal  tract  is  often  in- 
fested with  large  numbers  of  echinococci. 
The  eggs  that  are  passed  with  the  stools 
find  their  way  into  the  food,  thence  to 
the  stomach  of  man  ;  as  the  embrj'o 
hatches  it  enters  the  blood,  is  carried  to 
the  liver  or  kidneys,  where  it  forms  the 
hydatid  cyst.  This  disease  is  most  com- 
mon in  the  arctic  regions,  where  the 
natives  live  with  their  dogs,  and  it  is 
said  that  in  Iceland  approximately  one- 
seventh  of  the  mortality  is  due  to  hydatid 
disease. 

Ejistrongylus  Gigas. — The  presence  of 
this  parasite  in  the  urine  is  a  very  rare  oc- 
currence. According  to  the  researches 
of 'Leuckart.i  the  existence  of  this  para- 
site in  man  is  a  matter  of  some  doubt. 

Ascaridcs. — In  rare  instances  ascarides 
have  been  found  in  the  urinary  passages 
in  the  urine  is  usually  explained  by  an  abnormal  communi- 
cation between  the  intestine  and  the  urinary  tract.  Scheiber  ^ 
reports  having  found  in  the  urine  of  a  woman  worms  that  he 
considered  had  been  derived  from  the  genital  organs,  and  he 
has  named  them  rliabditis  o-cnitalis. 


»w4'> 


\--m 


Fig.  52. — Taenia 
echinococcus,  enlarg- 
ed. Above,  at  the 
right,  echinococcus 
of  natural  size  (after 
Heller). 


Their  presence 


1  Leuckart,  "  Deutsche  med.  Wochenschr.,"  xni,  S.  390. 

2  Scheiber,  "  Virchow's  Archiv,"  Lxxxn,  161,  1884. 


CHAPTER  VII. 

URINARY  CONCRETIONS, 

Urinary  concretions  or  calculi  consist  of  an  aggregation 
of  solid  matter  that  has  becorne  separated  or  precipitated 
from  the  urine.  They  may  form  in  any  part  of  the  urinary 
tract,  from  the  tubules  of  the  kidney  to  the  meatus  urina- 
rius.  They  vary  very  much  in  their  composition,  but  in- 
variably consist  of  certain  constituents  of  the  urine — either 
normal  or  pathologic — that  have  separated  or  become  pre- 
cipitated from  it.  The  nucleus  may,  however,  consist  of  a 
foreign  body  that  has  been  introduced  into  the  urinary  pas- 
sages, or  of  certain  substances  that  have  their  nativity  in 
the  body,  such  as  mucous  or  blood  coagula,  or  fragments 
of  morbid  tissue  that  have  become  detached.  Of  the  for- 
eign substances  that  have  been  found  to  form  the  nucleus 
of  urinary  calculi  may  be  mentioned  peas  or  beans  that 
have  been  introduced  into  the  urethra  by  the  insane  or  by 
children,  pieces  of  catheters  or  bougies  that  have  been  acci- 
dentally broken  off  in  the  urethra  or  bladder,  pieces  of  soap 
or  candles,  hanpins,  pins,  needles,  and  bullets  that  have 
lodged  in  some  portion  of  the  urinary  tract.  From  this 
it  is  seen  that  the  nucleus  of  a  urinary  calculus  may  be  any 
substance  that  has  its  origin  in  the  body  and  that  exists  in 
solid  form  in  the  urinary  passages,  or  a  foreign  body  that 
may  have  been  accidentally  or  intentionally  introduced  into 
them. 

The  conditions  of  the  urine  favoring  the  growth  of  calculi 
are  variable.  Among  the  causes  may  be  mentioned  (i)  a 
diminution  in  the  amount  of  water  excreted  ;  (2)  a  change 
in  the  reaction  of  the  urine,  whether  abnormally  acid  or 
alkaline  ;  (3)  an  increased  formation  of  some  of  the  less 
easily  soluble   constituents  of  the  urine.      Changes  in  the 

270 


URINARY  CONCRETIONS.  271 

reaction  embrace  hyperacidity,  which  favors  the  deposition 
of  uric  acid  and  urates  and  of  calcium  oxalate  by  diminish- 
ing the  solvent  action  of  the  urine  over  these  substances  ; 
and  an  alkaline  condition  of  the  urine,  which  causes  the 
separation  of  the  phosphates  and  carbonates  of  calcium 
and  magnesium  and  of  ammonium  urate.  The  chief  effect 
of  an  increased  acidity  of  the  urine  is  to  lessen  the  solu- 
bility of  the  uric  acid  by  diminishing  the  amount  of  alkali 
with  which  it  may  enter  into  combination.  Uric  acid  is 
usually  present  in  the  urine  in  solution  in  the  form  of  nor- 
mal urate  of  sodium  or  potassium,  which  is  very  soluble  in 
water.  In  case  the  uric  acid  is  deprived  of  a  part  or  the 
whole  of  its  base,  either  the  acid  urate  of  potassium  or 
sodium  or  uric  acid  is  the  result.  These  substances,  being 
much  less  soluble  in  water  than  the  normal  urates,  separate 
from  the  urine,  and  tend  to  become  aggregated  in  the  form 
of  concretions.  An  alkaline  reaction  of  the  urine  may  be 
due  to  the  presence  of  either  a  fixed  alkali  or  to  free  am- 
monia and  ammonium  carbonate.  It  rarely  happens  that  a 
calculus  forms  as  a  result  of  a  deposition  of  the  earthy 
phosphates  by  a  fixed  alkali,  as  is  well  demonstrated  in 
those  cases  in  which  alkaline  remedies  are  given  for  a  long 
time,  as  in  the  treatment  of  acute  rheumatism,  and  also  in 
those  cases  in  which  the  urine  is  habitually  alkaline,  as  in 
some  cases  of  faulty  metabolism. 

Of  much  greater  importance  is  an  ammoniacal  reaction 
that  frequently  results  in  a  calculus  formation  by  the  de- 
position of  triple  phosphate,  amorphous  phosphates,  and 
ammonium  urate.  (See  Reaction,  p.  31.)  Concretions  from 
this  cause  are  quite  commonly  met  with  in  cases  of  irritation 
or  inflammation  of  the  bladder,  the  change  from  a  normally 
acid  to  an  alkaline  reaction  being  due  to  the  presence  of  the 
urea  ferment  that  decomposes  the  urea.  A  deposit  of  phos- 
phates always  tends  to  increase  the  size  of  any  calculi  that 
may  already  exist. 

A  diminution  in  the  amount  of  water  excreted,  particu- 
larly when  coupled  with  an  increased  formation  of  any  of 
the  slightly  soluble  constituents  of  the  urine,  such  as  uric 
acid  and  acid  urates,  calcium  oxalate,  cystin,  and  very  rarely 
xanthin,  favors  the  tendency  to  the  formation  of  concretions 
within  the  urinary  passages,  since  these  substances  do  not 
find  a  sufficient  amount  of  urine  to  hold  them  in  solution. 


272  URINARY  SEDIMENTS 


CONSTITUENTS  OF  URINARY  CALCULI. 

These  are  either  organic  or  inorganic  or  a  mixture  of 
the  two.  They  are  conveniently  divided  into  two  classes, 
as  follows:  (i)  Primary  coistitiioits,  or  those  which  sepa- 
rate from  the  urine  without  any  material  change  in  the 
character  of  the  urine,  other  than  changes  referable  to 
altered  metabolism  ;  and  (2)  secondary  constituents,  or  those 
which  separate' from  the  urine  as  a  result  of  ammoniacal 
fermentation. 

'  Primary  Constituents.  Secondary  Constituents. 

!  sodium, 
ammonium, 
potassium.         Calcium  phosphate, 
calcium, 
magnesium. 
Calcium  oxalate.  Calcium  carbonate. 

Calcium   phosphate,  both  crystalline       Ammonio-magnesium    phosphate 

and  amorphous.  (triple  phosphate). 

Calcium  carbonate.  Ammonium  urate. 

Cystin. 
Xanthin. 
Indigo. 

Urostealith  (Heller). 
Silica. 
Albuminous   substances   (blood,  pus, 

etc.). 
Bilirubin  (hematoidin). 

Urate  of  ammonium,  calcic  carbonate,  and  calcic  phos- 
phate may,  therefore,  be  either  primary  or  secondary  con- 
stituents. 

Urinary  concretions  are  most  commonly  found  in  the 
pelvis  of  the  kidney  and  in  the  bladder,  but  they  may  form 
in  any  part  of  the  urinary  tract.  In  the  Warren  Museum 
at  the  Harvard  Medical  School  is  a  rare  specimen  showing 
a  number  of  medium-sized  concretions  in  the  pelves  of  both 
kidneys  and  in  both  ureters,  also  a  large  calculus  in  the 
bladder.  Calculi  are  also  sometimes  formed  in  sinuses  con- 
necting the  urinary  passages  with  the  intestines,  uterus,  or 
vagina. 

The  nnniber  of  concretions  that  may  be  present  in  the 
urinary  passages  is  almost  unlimited  ;  often  there  is  only  a 
single  stone,  but  there  may  be  several  hundreds. 

Urinary  concretions  vary  in  size  from  that  of  a  pinhead 
to  that  of  an  orange  or  even  larger.     Those  of  small  size 


CONSTITUENTS  OF  URINARY  CALCULI.  273 

have  been  somewhat  arbitrarily  termed  sa)id  or  gravel, 
while  those  of  large  size  are  called  stones  or  calculi.  The 
size  of  a  calculus  is  limited  only  by  the  dimension  of  the 
cavity  in  which  it  is  formed.  The  smaller  concretions 
usually  emanate  from  the  kidney  or  pelvis  of  the  kidney, 
while  those  of  large  size  generally  come  from  the  bladder. 
Concretions  vary  in  weight  from  a  few  milligrams  to  .several 
grams  ;  in  the  Dupuytren  Museum,  at  Paris,  is  a  calculus 
weighing  i  596  grams. 

T\\&  surf  ace  of  a  urinary  calculus  varies  with  its  composi- 
tion and  its  location  in  the  urinary  tract.  Those  consisting 
of  uric  acid,  phosphates,  and  cystin  are  usually  smooth, 
while  those  made  up  of  calcium  oxalate  are  generally 
rough  and  lobulated — vmlberry  calculi.  In  case  several 
concretions  occupy  a  single  cavity — for  example,  the 
bladder — their  surfaces  are  often  polished  in  those  portions 
that  rub  against  each  other  during  the  natural  movements 
of  the  bladder  wall  or  during  the  changes  in  position  of  the 
body.      The  smooth  or  polished  surfaces  are  termed  facets. 

The  shape  of  urinary  calculi  varies  as  the  location.  Those 
in  the  kidney  proper  are  generally  very  irregular  ;  they 
often  have  small  projections  that  have  extended  into  cavities 
formed  by  the  destruction  of  the  renal  tissue.  Calculi  in 
the  pelvis  of  the  kidney  when  large  usually  assume  the 
form  of  that  cavity,  projections  taking  place  into  the  calices, 
and  giving  the  calculus  in  some  cases  a  shape  not  unlike 
that  of  an  elephant ;  small  concretions  in  the  pelvis  are 
generally  round  or  oval.  Calculi  in  the  bladder  vary 
greatly  in  shape.  If  only  a  single  concretion  be  present,  it 
is  usually  round,  oval,  or  sometimes  flat.  If  numerous 
calculi  are  present,  their  form  may  be  modified  by  constant 
pressure  against  each  other.  Occasionally,  a  calculus 
becomes  partially  encysted  in  the  bladder,  so  that  the 
deposit  takes  place  only  upon  one  portion,  thereby  causing 
the  growth  of  the  calculus  to  take  place  in  one  direction 
only,  and  giving  it  a  very  irregular  shape.  Those  that 
have  formed  in  the  urethra  are  generally  oblong  or  cylindric 
in  shape,  and  when  there  are  several,  the  ends  of  those  that 
are  adjacent  are  often  highly  polished. 

The  color  of  calculi  varies  with  their  composition  and  the 

admixture  of  organic  subtsances  such  as  blood,  pus,  fibriri, 

etc.     Those  consisting  of  uric  acid  and  urates  are  always 

colored,  varying  between  a  pale  straw  and  a  dark  brown, 

18 


274  URINARY  SEDIMENTS. 

the  coloring-matter  being  derived  chiefly  from  the  urine. 
Calculi  consisting  of  calcium  oxalate  are  often  of  a  dark- 
brown  color  due  chiefly  to  the  presence  of  decomposed 
blood  and  of  fibrin.  Phosphatic  calculi  are  generally  gray- 
ish or  white,  while  those  made  up  of  cystin  are  usually  yellow 
in  color. 

The  composition  of  urinaiy  calculi  may  be  simple,  con- 
sisting of  only  one  constituent  of  the  urine,  such  as  uric 
acid  or  calcium  oxalate,  or  it  may  be  compoiind,  with  two 
or  more  primary  deposits  occurring  in  separate  and  alternate 
layers,  the  most  common  of  these  constituents  being  uric 
acid  and  calcium  oxalate.  Several  of  the  constituents  may 
be  mixed  in  any  portion  of  the  stone.  It  is  not  uncommon 
to  find  a  calculus  with  a  central  portion  composed  of  alter- 
nate layers  of  two  or  more  of  the  primary  constituents  and 
an  outer  layer  of  some  one  of  the  secondary  constituents. 

Most  urinary  calculi  consist  of  three  distinct  parts — i.  e., 
the  nucleus  ;  the  body  ;  and  the  crust.  The  nucleus  occu- 
pies the  center  and  may  have  the  same  composition  as  the 
rest  of  the  concretion,  but  it  often  consists  of  some  albu- 
minous body,  such  as  a  coagulum  of  fibrin,  or  mucus  or 
pus  mixed  with  uric  acid,  urate,  or  calcium  oxalate  crystals 
about  which  are  deposited  other  similar  or  perhaps  entirely 
different  urinary  constituents.  A  concretion  may  have 
several  nuclei,  as,  for  example,  when  two  or  more  small 
calculi  become  united  to  form  a  single  stone  ;  these  nuclei 
are  readily  seen  when  a  section  is  made  through  the  calcu- 
lus. The  nucleus  varies  much  in  size  and  usually  occupies 
the  center  of  the  concretion,  but  it  may  be  excentrically 
placed  especially  if  the  growth  of  the  calculus  is  only  in 
one  direction. 

The  body  comprises  the  greater  part  of  the  calculus  and 
surrounds  the  nucleus  ;  it  may  or  may  not  have  the  same 
composition  as  the  nucleus.  The  body  may  consist  of 
concentric  layers  of  two  or  more  urinary  constituents,  such 
as  a  layer  of  uric  acid  and  urates,  another  of  calcium  oxa- 
late, and  so  on  for  several  layers.  The  several  layers  of  the 
body  may  be  differently  colored  ;  even  those  having  the 
same  composition  may  be  variously  colored. 

The  crust  or  external  envelop  of  the  calculus  is  deposited 
upon  the  body,  and  always  consists  of  one  or  more  of  the 
secondary  constituents  of  the  urine,  the  phosphates  usually 
predominating  ;  in  other  words,  the  crust  is  always  found 


URIC  ACID  AND  URATE  CONCRETIONS.  275 

after  ammoniacal  fermentation  of  the  urine  has  taken  place, 
and  it  usually  forms  upon  v^esical  calculi.  Concretions  that 
have  formed  in  an  acid  urine  do  not,  therefore,  have  a  crust. 
Calculi  that  have  smooth  surfaces  like  the  uric  acid  and 
urate  may  not  havx  a  crust  formation  even  when  present  in 
an  ammoniacal  urine,  but  calculi  consisting  of  calcium  oxa- 
late, on  account  of  their  rough  surfaces,  usually  have  a  crust 
formation  and  sometimes  the  deposit  begins  while  they  are 
quite  small.  As  a  rule,  the  time  required  for  the  beginning 
of  formation  of  a  crust  depends  largely  upon  the  time  nec- 
essary for  the  calculus  to  produce  a  cystitis. 


URIC  AQD  AND  URATE  CONCRETIONS.     . 

Calculi  consisting  partly  or  entirel}-  of  uric  acid  and 
urates  comprise  the  great  majority  of  concretions  found 
in  the  urinary  tract.  They  are  very  common  as  renal 
calculi  in  children,  especially  those  consisting  chiefly  of 
ammonium  urate.  They  are  generally  smooth,  oval,  or 
round  and  of  a  yellow  or  brown  color.  When  such  con- 
cretions are  formed  in  the  kidney  or  pelvis  of  the  kidney, 
they  may  be  washed  out  with  the  urine  singly  or  in  num- 
bers, and  are  then  found  to  vary  in  size  from  a  pinhead  to 
that  of  a  kernel  of  wheat,  or  to  that  of  a  pea.  Their  pas- 
sage down  the  ureter  is  accompanied  by  more  or  less  pain, 
so  acute  at  times  as  to  cause  the  symptoms  of  renal  colic. 
If  these  small  concretions  are  retained  in  the  bladder,  they 
usually  grow  more  or  less  rapidly,  and  then  instead  of  being 
perfectly  smooth  are  often  irregular,  and  vaiy  in  weight  from 
a  few  grains  to  several  ounces.  When  uric  acid  and  urate 
concretions  are  forming,  the  urine  is  usually  found  to  be 
concentrated,  highly  colored,  of  strongly  acid  reaction,  and 
of  high  specific  gravity.  The  sediment  generally  contains 
crystals  of  uric  acid  or  the  hedgehog  forms  of  acid  ammo- 
nium urate,  or  the  stellate  groups  of  sodium  urate  ;  there  is 
usually  also  evidence  of  more  or  less  irritation  of  the  kid- 
neys and  frequently  signs  of  mechanical  irritation  of  the 
bladder  that  has  been  set  up  by  the  crx^stalline  elements. 

Concretions  that  consist  chiefly  of  urates  do  not  usually 
attain  the  large  size  of  the  mixed  uric  acid  and  urate  calculi, 
rarely  being  found  larger  than  an  average  sized  marble. 
They  are  usually  lighter  in  color  and  not  so  hard  as  the 


276  URINARY  SEDIMENTS. 

mixed  concretions.  When  .some  of  the  powdered  calculus 
is  heated  on  platinum  foil,  it  chars  and  completely  disap- 
pears if  uric  acid  or  ammonium  urate  be  the  only  constituent ; 
but  if  sodium  urate  be  present,  there  remains  a  residue  that 
is  soluble  in  water  and  has  an  alkaline  reaction  (carbonate 
of  the  alkali). 


CALCIUM  OXALATE  CONCRETIONS. 

These  are  met  with  most  often  as  medium  or  large,  dark 
brown,  rough,  trabeculated  bodies  having  a  mulberry-like 
surface,  hence  the  name  "  inidbcrry  calculi.'"  They  are  very 
hard  and  can  be  crushed  only  with  difficulty.  Calcium  oxa- 
late concretions  are  composed  chiefly  of  calcium  oxalate 
which  is  mixed  with  more  or  less  organic  matter.  Occasion- 
ally the  body  of  the  calculus  consists  of  alternating  layers 
of  calcium  oxalate  and  uric  acid.  The  nucleus  often  consists 
of  uric  acid  and  urates,  or  a  coagulum  of  blood  or  mucus  ; 
it  may,  however,  be  made  up  entirely  of  calcium  oxalate. 
As  previously  stated,  calcium  oxalate  concretions  are  very 
apt  to  have  a  crust  consisting  chiefly  of  phosphates. 

The  characteristics  of  the  urine  from  which  oxalate  con- 
cretions are  being  deposited  are  very  much  the  same  as 
when  uric  acid  and  urate  concretions  are  forming.  The 
sediment  will  contain  crystals  of  calcium  oxalate  and  evi- 
dences of  a  more  or  less  marked  irritation  of  the  kidneys 
and  bladder.  If  the  stone  is  forming  in  the  bladder,  a 
typical  chronic  cystitis  may  exist.  When  some  of  the  pow- 
dered calculus  is  heated  on  platinum  foil,  it  chars  slightly, 
on  account  of  the  organic  matter  that  is  mixed  with  it ;  there 
remains  a  white  residue  of  calcium  oxide  or  calcium  car- 
bonate, according  to  the  amount  of  heat  used.  If  the 
former,  it  will  be  found  to  be  only  slightly  soluble  in  a 
drop  of  water,  which  will  have  an  alkaline  reaction  ;  if  the 
latter,  it  will  dissolve  with  effervescence  in  a  drop  of  acetic 
acid. 


PHOSPHATIC  CONCRETIONS. 

\         These  always  form  in  neutral  or  alkaline  (ammoniacal) 
urine  and  originate  chiefly  in  the  bladder.     They  are  usually 


CALCIUM  CARBONATE  CONCRETIONS.  277 

white  or  of  a  grayish  color,  quite  soft  and  easily  crushed. 
They  are  often  covered  on  their  surface  with  bright,  glisten- 
ing points  representing  large  crystals  of  triple  phosphate. 
The  surface  may  be  smooth  or  rough  ;  if  it  is  smooth  it 
frequently  has  the  feeling  of  chalk.  Phosphatic  concre- 
tions having  a  grajash  color  are  usually  harder  than  the 
white  or  chalky  calculi.  The  former  consist  chiefly  of  cal- 
cium phosphate,  while  the  latter  are  composed  chiefly  of 
triple  phosphate.  Concretions  that  consist  solely  of  cal- 
cium phosphate,  or  triple  phosphate  are  very  uncommon,  the 
mixed  phosphatic  calculus  being  the  one  met  with  most  fre- 
quently. 

If  some  of  the  powdered  calculus  be  heated  on  platinum 
foil  it  does  not  char  or  burn,  but  a  bulky  residue  remains 
which  dissolves  in  acetic  acid  without  effervescence,  as  does 
the  original  powder. 


CALCIUM  CARBONATE  CONCRETIONS. 

Concretions  composed  of  calcium  carbonate  are  very  rare 
in  man,  very  few  cases  having  been  reported.  They  are  not 
uncommon  in  the  herbivora.  They  are  usually  small,  of  a 
grayish  color,  of  smooth  surface  and  very  hard.  Calcium 
carbonate  concretions  are  generally  spherical  in  shape,  and 
on  section  they  present  concentric  lines.  When  some  of 
the  original  powder  is  treated  with  a  drop  of  acetic  acid  it 
dissolves  with  effervescence  ;  when  the  powder  is  heated  on 
platinum  foil  to  a  white  heat  it  is  converted  into  calcium 
oxide,  which  is  but  slightly  soluble  in  a  drop  of  water,  the 
solution  having  an  alkaline  reaction. 


CYSTIN  CONCRETIONS. 

These  are  among  the  rarer  forms  of  calculi.  They  are 
quite  soft  and  of  a  pale-yellow  color.  As  a  rule,  they  are 
oval  or  cylindric  in  shape  with  a  rough — finely  granular — 
surface.  They  may  form  in  the  kidneys  or  bladder,  the 
latter  location  being  perhaps  the  more  common. 

Cystin  calculi  when  taken  from  the  body  usually  have  a 
yellow  color  not  unlike  beeswax,  but  after  being  exposed 


278  URINARY   SEDIMENTS. 

to  the  light  for  a  long  period  the  color  changes  to  a  green. 
They  are  generally  of  light  weight  and  vary  much  in  size. 

Probably  the  largest  cystin  calculus  in  existence  is  the 
one  reported  by  Dr.  E.  S.  Wood.^  It  was  removed  from 
the  bladder  by  Dr.  J.  C.  Warren,  and  weighed,  after  drying, 
101.883  grams.  It  was  in  the  form  of  a  flattened  oval,  and 
measured  2^X2^X1^  inches. 

Upon  section  they  are  found  to  be  crystalline  and  present 
a  radiating  appearance.  When  some  of  the  powdered  cal- 
culus is  heated  on  platinum  foil  it  burns  with  a  blue  flame, 
and  the  odor  of  burning  sulphur  is  evolved  ;  no  residue 
remains  after  ignition.  Cystin  is  recognized  by  its  solubility 
in  alkaline  hydrates  and  in  strong  acids,  also  by  its  insolu- 
bility in  acetic  acid.  If  some  of  the  powder  be  treated  w^ith 
a  drop  of  ammonic  hydrate  on  a  glass  slide,  it  will  dissolve  ; 
and  if  the  mixture  be  allowed  to  stand  until  the  ammonia 
has  escaped,  the  residue  will  be  found  to  consist  of  the 
colorless  hexagonal  cr^^stals  of  cystin. 


XANTHIN  CONCRETIONS. 

These  are  very  rare,  being  probably  the  rarest  of  all  of 
the  urinary  calculi.  They  may  consist  entirely  of  xanthin, 
or  the  xanthin  may  be  mixed  with  uric  acid  and  urates. 
The  cases  of  xanthin  calculi  thus  far  reported  have  occurred 
in  children.  Xanthin  concretions  vaiy  in  color  from  a  white 
or  pale  yellow  to  a  brown,  and  they  range  in  size  from  a 
bean  to  a  hen's  egg. 

When  some  of  the  powdered  calculus  is  heated  on  plati- 
num foil,  it  chars  and  entirely  disappears  ;  in  this  respect  it 
resembles  uric  acid.  But  xanthin  can  readily  be  distin- 
guished from  uric  acid  by  a  modification  of  the  murexide 
test  (see  p.  66).  If  some  of  the  powdered  calculus  be 
treated  with  a  drop  of  nitric  acid  on  a  porcelain  surface 
and  evaporated  to  dryness,  and  the  residue  treated  with  a 
drop  of  potassic  hydrate,  a  pinkish  tint  appears  which,  if 
xanthin  be  present,  deepens  to  a  violet  on  warming.  Uric 
acid  gives  a  violet  with  potassic  hydrate,  the  color  disap- 
pearing on  w^arming. 

1  "  Journ.  Boston  Soc.  Med.  Sciences,"  Feb.,  1898,  p.  82. 


INDIGO  CONCRETIONS.  279 


INDIGO  CONCRETIONS. 


These  are  also  exceedingly  rare.  Ord  ^  has  reported  a 
case  in  which  an  indigo  calculus  was  found  in  the  pelvis  of 
the  right  kidney  of  a  woman  whose  left  kidney  was  de- 
stroyed by  sarcoma.  The  stone  weighed  40  grams,  and 
had  a  nucleus  consisting  of  a  coagulum  of  blood  and  a 
deposit  of  calcium  phosphate.  Indigo  derived  from  a  de- 
composition of  the  indican  of  the  urine  was  deposited  upon 
one  side  of  the  calculus.  Forbes  2  has  also  reported  an 
indigo  calculus  w^hich  was  found  in  the  pelvis  and  a  calyx 
of  one  kidney.  The  stone  weighed  147  grains  ;  its  greatest 
thickness,  fore  and  aft,  was  if  of  an  inch  ;  it  measured 
across  its  base  i  ^  inches,  and  from  base  to  apex  i  y.  inches. 
It  was  dark  brown  in  color  ;  and  when  it  was  drawn  across 
white  paper,  it  left  a  rough,  blue  mark.  The  specimen  can 
be  seen  in  the  Museum  of  Jefferson  Medical  College,  Phila- 
delphia. 

So  far  as  the  author  is  aware  these  two  cases  of  indigo 
calculus  are  the  only  ones  that  have  thus  far  been  recorded. 


UROSTEALITH  CONCRETIONS. 

Urostealith,  or  fatty  concretions,  are  very  rare.  They  are 
soft  and  elastic  when  fresh  ;  but  when  dry  they  are  hard 
and  brittle.  They  are  generally  of  a  yellowish  or  brown- 
ish color,  and  are  frequently  enclosed  within  a  phosphatic 
crust.  When  some  of  the  calculus  is  heated  on  platinum 
foil  it  burns  with  a  yellow  flame  and  gives  off  an  odor  not 
unlike  that  of  benzoin  or  shellac. 


FIBRIN  OR  BLOOD  CONCRETIONS. 

These  are  formed  as  a  result  of  the  coagulation  of  blood 
in  the  urinary  tract.  They  are  commonly  found  as  nuclei 
of  other  calculus  growths,  and  not  infrequently  contain  a 
deposit  of  uric  acid,  calcium  oxalate,  or  phosphates.   When 

1  Ord,  "Influence  of  Colloids  upon  Crystalline  Form  and  Cohesion  in 
Urinary  and  Other  Calculi,"  London,  1879,  p.  144. 

2  "Medical  News,"  Aug.  18,  1894. 


280  URINARY  SEDIMEN'JS. 

portions  of  calculi  containing  a  large  proportion  of  organic 
matter  are  heated  on  platinum  foil,  they  give  off  the  odor 
of  burnt  horn  and  burn  with  a  yellow  flame. 

Concretion?  containing  crystals  of  Jicuiatoidin  are  occa- 
sionally seen.  These  crystals  are  most  commonly  seen  in 
fibrin  concretions,  or  in  those  calculi  that  have  formed  in 
the  presence  of  a  considerable  amount  of  blood. 


PROSTATIC  CONCRETIONS. 

Concretions  emanating  from  the  follicles  of  the  prostate 
are  occasionally  discharged  with  the  urine.  They  usually 
have  a  laminated  nucleus  consisting  of  amyloid  bodies  {cor- 
pora ainylacecB)  about  which  is  deposited  a  mixture  of 
ammonio-magn.esium  phosphate  and  calcium  phosphate. 
They  do  not,  as  a  rule,  produce  symptoms  until  they  have 
attained  a  large  size  ;  prostatic  concretions  of  large  size  are, 
however,  rare. 


CHEMIC  EXAMINATION  OF  URINARY  CALCULI. 

Before  beginning  the  chemic  examination  of  a  calculus, 
its  size,  shape,  color,  and  density  should  be  observed,  as 
these  properties  often  suggest  the  probable  composition  of 
the  concretion.  Since  a  calculus  may  consist  of  alternate 
layers  of  two  or  more  substances,  it  is  first  necessary  to 
make  a  section  through  the  center  of  each  layer  of  the 
stone  by  sawing,  in  order  to  determine  the  composition  of 
each  layer.  If  several  different  layers  are  found,  it  is  essen- 
tial that  a  portion  of  each  layer  be  subjected  to  chemic  ex- 
amination ;  that  portion  to  be  tested  should  always  be  in 
the  form  of  a  fine  powder,  which  can  be  obtained  by  scraping 
a  very  small  amount  of  the  stone  from  its  cut  surface  by 
means  of  a  knife-blade,  or  by  placing  small  particles  of  the 
calculus  in  a  mortar  and  grinding  them  to  a  powder  with  a 
pestle.  If  the  section  of  the  stone  is  found  to  have  a 
homogeneous  appearance,  it  is  only  necessary  to  examine 
the  sawdust ;  it  is,  however,  advisable  to  make  a  separate 
examination  of  the  nucleus  in  every  instance,  since  this  por- 
tion of  a  concretion  is  subject  to  marked  variation. 

The  chemic  examination  is  best  conducted  in  the  follow- 
ing manner  : 


CHEMIC  EXAMINATION  OF  URINARY  CALCULI.         281 

1.  Preliminary  Examination. — Heat  on  platinum  foil : 
Albumin  =  a  flame  with  odor  of  burnt  horn. 
Urostealith  =;  a  flame  with  odor  of  shellac  and  benzoin. 
Cystin  ^=  a  blue  flame  with  odor  of  SO^. 

Xanthin  and  uric  acid  =  char  without  a  flame. 

Alkaline  urates  ::=  alkaline  residue  soluble  in  H^O. 

Earthy  phosphates  =  a  residue  soluble  in  acetic  acid  with- 
out effervescence. 

Calcium  oxalate  and  calcium  carbonate  =  a  residue  soluble 
in  acetic  acid  zvith  effervescence. 

Calcium  carbonate  =  original  powder  soluble  in  acetic 
acid  with  effervescence. 

Calcium  oxalate  =^ox\g\\\z\.  powder  insoluble  in  acetic  acid. 

Silica  ^  residue  insoluble  in  HCl. 

Murexide  Test  for  Uric  Acid. — Original  powder  -f  HNO^ 
and  evaporate  =  pink  residue  -f-  NH^OH  =  purple 
color  =  uric  acids  and  urates. 

Original  powder  +  HNOj  and  evaporate  -)-  KOH 
=  violet  color,  which  disappears  on  heating  =  uric 
acid.     Violet  increases  on  heating  =  xanthin. 

2.  Systematic     Examination. — Presence   of    uric    acid 

shown  by  (  i).     Boil  in  H^O  and  filter. 

A.  Filtrate  -[-  HCl.      Let   stand    24°  =  crystals  of  uric 

acid.     Bases  in  solution.     Concentrate. 

Calcium  urate  =  one  drop  of  solution  -f-  solution  ammo- 
nium oxalate  =  crystals  calcium  oxalate. 

Magnesium  urate  =  one  drop  of  solution  -|-  NH^OH  -j- 
Na^HPO^  :^  crystals  ammonio-magnesium  phosphate. 

Sodium  urate  =  one  drop  of  solution  -(-  Pt.Cl^  =  after 
concentrating,  prisms  of  sodioplatinic  chloride. 

Potassium  urate  a.nd  ammonium  urate  =  one  drop  of  solu- 
tion -f-  Pt.Cl^  :=  dodecahedra  of  potassioplatinic 
chloride  and  ammonioplatinic  chloride. 

Potassium  Urate. — Evaporate  solution  and  igniteon  mica. 
Residue  -|-  HCl  -)-  Pt.  Cl^=  potassioplatinic  chloride. 

A?nmotiium  Urate. — Evaporate  solution  and  ignite  on 
mica.      Residue  =  no  crystals  with  Pt.  CI^. 

B.  Portion  insoluble  in  H^O.     Add  HCl. 
Uric  acid  =  insoluble. 

Calcium  carbonate  =  soluble  with  effervescence.  Filter  + 
NH^OH  1=  precipitate  of  calcium  oxalate,  calcium 
phosphate,  and  ammonio-magnesium  phosphate. 
Wash.  Calcium  oxalate  =  insoluble  in  acetic  acid. 
Filter  +  ammonium  oxalate  to  filtrate.  Calcium 
phosphate  gives  precipitate  of  calcium  oxalate.  Fil- 
ter -f-  NH^OH  to  filtrate  =  precipitate  of  ammonio- 
magnesium  phosphate. 


PART  II. 
DIAGNOSIS. 


CHAPTER  VIII. 

DISTURBANCES  AND  DISEASES  OF  THE 
KIDNEYS. 

ACTIVE  HYPEREMIA. 

Active  hyperemia — active  congestion — is  essentially  not 
a  disease  of  the  kidneys,  but  a  disturbance  of  the  functions 
of  these  organs.  This  condition  is  invariably  due  to  the 
presence  of  some  irritant  that  is  within  or  is  passing  through 
the  kidneys,  or  to  some  alteration  in  their  circulation — in 
other  words,  it  is  always  secondary  in  its  nature. 

Causes. — The  causes  of  active  hyperemia  may  be  divided 
into  three  general  classes  : 

I.  Any  general  disease  or  disturbance,  which  is  not 
primarily  renal,  but  which  may  cause  a  change  in  the 
renal  circulation,  as  in  severe  nervous  diseases,  notably 
delirium  tremens  and  acute  mania  ;  also  in  other  serious 
affections  that  act  by  causing  a  change  in  the  pressure  of 
the  blood  in  the  renal  vessels. 

Exposure  to  cold  and  wet  may  set  up  an  active  hyperemia 
of  the  kidneys  or  an  acute  nephritis.  The  reason  for  a 
renal  disturbance  under  such  circumstances  probably  is  that 
the  superficial  blood-vessels  and  the  capillaries  of  the  skin 
suddenly  contract,  due  to  vasomotor  changes,  congesting 
the  internal  organs,  and,  since  the  function  of  the  skin  is 
interfered  with,  the  renal  congestion  is  augmented  by  the 
necessity  for  increased  activity  of  the  kidneys. 

II,  Irritants  \A^ithin  or  Passing  Through  the  Kid- 
neys.— These  may  be  divided  into  two  distinct  classes — 
viz.,  insoluble  and  soluble. 

282 


ACTIVE  HYPEREMIA.  283 

(a)  Insoluble  Irritants. — These  are  cr)'stalline  substances 
that  may  be  separated  from  the  urine  in  the  kidneys,  and 
may  set  up  a  mechanical  disturbance  in  the  renal  tubules — 
c.  g.,  uric  acid,  acid  ammonium  or  sodium  urate,  calcium 
oxalate,  acid  calcium  phosphate,  and  cystin. 

[b)  Soluble  Irritants. — Of  these  there  are — 

/.  The  toxines,  which  are  soluble  poisons  formed  and 
eliminated  during  the  progress  of  disease.  Their  irritating 
effect  is  especially  seen  in  the  acute  diseases — viz.,  pneu- 
monia, typhoid  fever,  erysipelas,  measles,  scarlet  fever,  diph- 
theria, acute  rheumatism,  acute  miliary  tuberculosis,  cere- 
brospinal meningitis,  malaria,  etc.;  and  not  infrequently  in 
chronic  diseases,  such  as  pulmonary  tuberculosis,  chronic 
rheumatism,  chronic  malaria,  etc.  Irritant  toxines  may  also 
be  formed  in  the  intestines  as  a  result  of  faulty  processes 
going  on  there.  These  are  absorbed  by  the  blood  and 
eliminated  by  the  kidneys,  causing  an  active  hyperemia. 
This  is  especially  seen  in  children  who  are  suffering  from 
diarrhea  or  an  enterocolitis. 

Toxines  may  also  be  formed  in  those  acute  and  chronic 
local  diseases  that  are  attended  with  suppuration,  notably 
urethritis,  prostatitis,  vesiculitis,  bone  diseases,  abscesses 
(from  which  there  is  absorption),  and  diseases  of  the  female 
genitalia,  the  disturbing  element  being  a  toxine  that  is  ab- 
sorbed from  the  seat  of  the  disease  by  the  blood  and  elimi- 
nated by  the  kidneys. 

2.  Drtigs. — The  elimination  of  any  irritating  drug,  such 
as  arsenic,  lead,  mercury,  cantharides,  salicylic  acid,  po- 
tassium chlorate,  phenol  and  its  compounds,  volatile  oils, 
etc. 

J.  Coricentrated  Urine. — Not  infrequently  the  passage  of 
a  concentrated  urine  sets  up  an  active  hyperemia  that  varies 
in  intensity  from  a  very  mild  condition  to  one  that  is  quite 
severe.  It  is  especially  seen  if  the  urine  has  been  in  a  state 
of  concentration  for  a  long  time.  An  active  hyperemia 
from  this  cause  rapidly  disappears  when  the  patient  is  given 
plenty  of  diluent  drinks,  the  urine  becoming  diluted  and 
less  irritating. 

^.  Bile. — This  substance  acts  as  an  irritant  in  its  way 
through  the  kidney.  It  is  obvious  that  the  merest  trace  of 
bile  would  not,  as  a  rule,  produce  more  than  the  slightest 
active  hyperemia,  whereas  larger  amounts  generally  set  up 
a  more  marked  form  of  this  disturbance. 


284      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

5.  Sugar. — What  has  been  said  of  bile  may  also  be 
credited  to  sugar.  The  author  has  yet  to  see  a  urine  con- 
taining bile  or  sugar — especially  if  one  or  the  other  were 
present  for  more  than  a  day  or  two  and  in  more  than  the 
slightest  trace — where  there  was  not  evidence  of  an  irrita- 
tion of  the  kidneys. 

III.  Irritants  Extending  Upward  from  the  Lower 
Urinary  Tract. — It  is  not  uncommon  to  have  a  gonorrheal 
inflammation  extend  upward  from  the  urethra  and  bladder, 
and  involve  the  straight  or  collecting  tubules  of  the  kidney. 
The  same  danger  exists  in  an  inflammation  of  the  bladder 
from  any  other  cause. 

In  case  there  is  some  obstruction  to  the  outflow  of  urine, 
as  by  a  urethral  stricture  or  an  enlarged  prostate,  the  col- 
lecting tubules  may  dilate,  and  finally  result  in  a  "surgical 
kidney." 

Various  bacteria,  more  especiall}'  tubercle  bacilli,  whether 
coming  from  the  lower  urinary  passages  by  extension  or 
by  way  of  the  blood-vessels,  may  set  up  a  focal  active 
hyperemia  of  the  kidneys.  The  disturbance  is  principally 
confined  to  the  pyramidal  portion  with  more  or  less  evi- 
dence of  extension  into  the  cortical  portion  of  the  kidney. 
Reference  will  again  be  made  to  this  under  the  heading  of 
Tuberculosis  of  the  Kidney. 

Character  of  the  Urine. — This  varies  as  the  cause  : 
i\  g.,  if  the  hyperemia  is  due  to  the  elimination  of  toxines 
that  are  produced  in  the  course  of  an  acute  febrile  dis- 
ease, we  will  generally  find  a  highly  colored,  concentrated 
urine,  whereas  if  the  cause  of  the  irritation  is  not  accom- 
panied by  fever,  the  urine  may  have  about  a  normal  con- 
centration, or  it  may  be  dilute. 

It  is,  of  course,  impossible  to  give  the  characteristics  of 
the  urine  that  will  apply  in  every  case  of  active  hyperemia, 
yet  a  few  general  rules  may  be  laid  down  concerning  the 
average  urine  in  this  disturbance. 

Quantity  in  Twenty-four  Hours. — Usually  less  than 
1500  c.c.  ;  average,  from  800  to  1200  c.c.  It  may  be  as 
low  as  300  or  400  c.c,  and  may  exceed  1500  c.c,  but  only 
for  a  short  time. 

Color. — Normal  or  high.  Not  infrequently  it  is  paler 
than  normal.  It  may  be  slightly  smoky  (usually  seen, 
however,  in  severe  active  hyperemia,  or  catarrhal  nephritis). 
(See  p.  286.) 


ACTIVE  HYPEREMIA.  285 

Reaction. — Almost  always  acid,  and  frequently  strongly 
acid. 

Specific  Gravity. — This  varies  according  to  the  metab- 
olism and  quantity  of  urine  ;  it  is  generally  normal  or  high 
(to 1 8  to  1030),  sometimes  less  than  normal.  It  usually 
bears  an  inverse  relation  to  the  quantity  of  urine  passed — 
e.g.,  quantity  of  urine  in  twenty-four  hours  800  c.c,  spe- 
cific gravity  103O;  or  quantity  2000  c.c,  specific  gravity 
1014.  This,  however,  is  not  always  the  case,  for  both  the 
quantity  and  specific  gravity  may  be  below  the  normal  at  the 
same  time — i\  ^.,  quantity   1200  c.c,  specific  gravity  1012. 

Normal  Solids  (Urea,  Uric  Acid,  Chlorides,  Phosphates, 
and  Sulphates). — Absolutely,  about  normal  or  slightly  di- 
minished, depending  upon  the  metabolism.  In  case  the 
metabolism  is  much  reduced,  as  by  an  acute  infectious  dis- 
ease, the  solids  may  be  found,  absolutely,  very  much  dimin- 
ished. In  diabetes  mellitus  they  are  usually  absolutely 
increased.  They  are  r'datively  increased  if  the  urine  is 
concentrated  ;  and  relatively  diminished  if  the  twenty-four- 
hour  quantity  is  near  the  normal  and  the  metabolism  is  low. 

Albumin. — The  quantity  varies  as  the  cause  and  the 
severity.  If  the  irritation  is  slight,  there  may  not  be  more 
than  the  slightest  possible  trace  or  a  slight  trace.  On  the 
other  hand,  if  the  hyperemia  is  severe,  as  following  expo- 
sure to  cold  and  wet,  the  quantity  of  albumin  may  go  as 
high  as  ^  of  I  per  cent.,  but  such  an  amount  rarely  con- 
tinues for  more  than  a  day  or  two,  when  it  will  fall  to  a  trace, 
slight  trace,  or  even  the  slightest  possible  trace.  (See  Severe 
Active  Hyperemia.)  Very  soon  after  the  removal  of  the 
cause  of  the  irritation  the  albumin  entirely  disappears,  but 
not'  until  all  of  the  renal  epithelium  that  has  been  denuded 
by  the  irritant  or  other  active  process  has  been  restored  to 
the -tubules. 

Sediment. — Usually  considerable  in  quantity,  and  in  the 
average  mild  case  consists  of  an  occasional  (or  few)  hyaline 
and  finely  granular  cast,  with  blood  and  renal  cells  adherent. 
An  occasional  (or  few)  free  renal  cell  and  blood  globule. 

If  crystalline  elements,  such  as  uric  acid  or  calcium 
oxalate,  are  the  cause  of  the  disturbance,  they  will  generally 
be  found  in  the  sediment,  and  occasionally  embedded  in  the 
casts.  Normal  blood  also  is  very  apt  to  be  found  under 
these  circumstances,  as  a  result  of  the  mechanical  irritation 
by  the  crystals. 


286      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

Long-continued  Active  Hyperemia. — If  the  source  of 
irritation  has  not  been  removed,  and  the  hyperemia  con- 
tinues for  months  or  years,  fatty  elements,  such  as  fatty  renal 
cells,  fat  drops  adherent  to  the  casts,  compound  granule  cells, 
and  rarely  a  small  fatty  cast,  may  be  found  in  the  sediment. 
These  fatty  changes  evidently  result  from  the  interference 
with  the  nutrition  of  the  renal  epithelium.  Besides  the  fatty 
elements  there  is  not  infrequently  a  little  more  abnormal 
blood  than  in  the  average  mild  hyperemia  of  short  duration. 

The  solids  will  usually  be  found  to  be  absolutely  more 
diminished  than  in  the  average  temporary  irritation. 

Severe  Active  Hyperemia  ("  Catarrhal  Nephritis"). — 
A  mild  active  hyperemia  may  gradually  or  suddenly  become 
intensified,  especially  during  the  progress  of  acute  infectious 
diseases,  and  a  mild  but  true  inflammatory  process  exist. 
A  severe  irritation  of  the  kidneys  may,  however,  be  severe 
from  the  start,  as  is  sometimes  seen  in  cases  of  exposure  to 
cold  and  zvct. 

Causes. — Any  of  the  causes  of  an  active  hyperemia 
already  enumerated  may  result  in  a  severe  renal  congestion  ; 
toxines  are  especially  liable  to  produce  this  condition. 

Character  of  the  Urine  in  the  Acute  Stage. 

Quantity. — Usually  below  the  normal — 600  to  looo  c.c. 

Color. — Smoky,  because  of  the  altered  blood  pigment 
(methemoglobin  or  hematin).  If  there  is  very  much  nor- 
mal blood  present,  the  urine  may  have  a  blood-red  color. 

Reaction. — Generally  strongly  acid.  It  may,  however, 
have  the  normal  acidity. 

Specific  Gravity. — This  varies  from  1018  to  1025 — in 
other  words,  not  far  from  the  normal.  Of  course,  if  the 
metabolism  is  much  diminished,  it  may  be  as  low  as  1012 
to  1015. 

Solids. — Absolute. — The  absolute  solids  are  usually  some- 
what below  the  normal,  but  dependent  upon  the  metabolism. 
In  pneumonia  they  may  be  high  during  the  first  fev/  days 
of  the  acute  stage,  but  later  on  they  may  be  very  low,  when 
not  only  the  metabolism  is  low,  but  there  is  a  serous  exuda- 
tion or  effusion,  into  which  to  a  greater  or  less  extent  the 
chlorides  and  urea  go.  Relative. — As  a  rule,  the  relative 
solids  are  about  normal.  They  may  be  a  little  high  or  even 
below  normal,  depending  upon  the  degree  of  concentration 
of  the  urine. 

Albuviin. — This  varies  in  quantity  from  a  slight  trace  to 


ACTIVE  HYPEREMIA.  287 

i^  of  I  per  cent.  The  large  quantity  of  albumin,  however, 
is  usually  present  only  for  a  short  period  (a  day  or  two), 
and  then  falls  to  about  a  trace.  The  comparatively  small 
quantity  of  albumin  (slight  trace  or  trace)  is  one  of  the 
important  elements  in  the  diagnosis  of  a  catarrhal  nephritis 
as  distinguished  from  an  acute  nephritis,  which  is  character- 
ized by  a  large  amount  of  albumin  (i^  to  i  ^^  per  cent.). 

Sediment. — Usually  considerable  in  quantity  and  consists 
chiefly  of  abnormal  blood  (possibly  some  normal  blood  if  the 
irritation  is  at  its  height) ;  few  (or  numerous)  granular  and 
brown  granular,  an  occasional  blood,  epithelial,  and  fibrin- 
ous cast ;  numerous  renal  epithelial  cells,  often  colored 
brown,  and  a  few  leucocytes. 

Frequently  there  is  evidence  of  a  coexisting  acute  in- 
flammation of  the  pelvis  of  the  kidneys,  in  which  case 
small  caudate  cells  from  the  superficial  layer  of  the  pelvis 
and  clumps  of  cells  from  the  caHces  will  be  found. 

Convalescence  from  a  Severe  Active  Hyperemia. — In 
the  severe  forms  of  active  hyperemia  or  catarrhal  nephritis 
there  is  frequently  a  distinct  convalescent  stage,  especially 
in  those  cases  in  which  the  source  of  irritation  has  been  partly 
or  entirely  removed  by  natural  means  or  by  treatment. 

Character  of  the  Urine. — Quantity. — The  quantity  is 
usually  found  to  be  above  the  average  normal  (1500  c.c), 
varying  from  1600  to  2000  c.c. 

Color. — Slightly  smoky  or  pale. 

Reaction. — Usually  acid,  unless  mild  diuretics,  such  as 
potassium  acetate,  may  have  been  taken,  when  the  reaction 
will  be  found  alkaline  from  fixed  alkalies. 

Specific  Gravity. — This  varies  as  the  twenty-four-hour 
quantity.     It  is  generally  between  10 12  and  10 18. 

Normal  Solids. — Absolute .  —  The  solids,  especially  the 
urea,  are  absolutely  about  normal.  If  for  any  reason  the 
patient  be  kept  on  a  low  diet,  of  course  the  solids  will  be 
absolutely  lower  than  when  a  liberal  amount  of  nitrogenous 
food  is  given.     Relatively,  the  solids  are  diminished. 

Albumin. — This  varies  from  the  slightest  possible  trace 
to  a  large  trace,  usually  the  former.  If  the  process  be  still 
rather  active,  the  albumin  may  reach  a  large  trace  (about 
yV  of  I  per  cent.). 

Sediment. — A  few  (sometimes  numerous)  abnormal  blood 
globules.  An  occasional  (or  few)  hyaline,  finely  granular, 
and  brown  granular  casts,  some  with  a  little  blood  and  fat, 


288      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

and  a  few  with  renal  cells  adherent.  Few  free  renal  cells,  an 
occasional  one  slightly  fatty. 

If  there  was  a  mild  pyelitis  during  the  acute  stage  of  the 
disturbance,  evidence  of  it  may  still  be  found — viz.,  little 
pus,  free  and  in  clumps  ;  small  round  cells,  free  and  in  the 
clumps  of  pus  ;  and,  possibly,  an  occasional  small  caudate 
cell  from  the  superficial  layer  of  the  pelvis  of  the  kidney. 
In  such  a  case  leucocytes  may  be  found  on  an  occasional 
cast,  especially  those  coming  from  the  straight  tubules. 

If  the  irritant  has  been  entirely  removed,  the  quantity  of 
urine  gradually  falls  to  the  normal,  the  casts  disappear  and 
finally  the  blood,  at  which  time  the  urine  will  be  found  free 
from  albumin — in  other  words,  complete  recovery. 

A  circumscribed  inflammation  of  one  or  both  kidneys 
may  take  place,  especially  as  a  result  of  the  extension  of  a 
gonorrheal  or  tubercular  inflammation  or  other  bacterial 
infection  of  the  bladder  and  lower  urinary  passages  to  the 
renal  pelvis,  and  then  to  circumscribed  areas  of  the  kidney. 
A  circumscribed  inflammatory  process  may  also  be  set  up 
around  a  crystalline  deposit  or  morbid  growth  in  the  kid- 
ney. Ijnder  these  circumstances  the  urine  has  the  usual 
features  of  an  active  hyperemia,  and  not  those  of  acute 
nephritis.    • 

There  are  very  few  clinical  symptoms  aside  from  the 
abnormal  features  of  the  urine,  which  are  directly  referable 
to  this  disturbance  of  the  kidneys.  In  the  majority  of  in- 
stances of  mild  active  hyperemia  renal  symptoms  are  entirely 
wanting.  Since  an  active  hyperemia  is  ahvays  secondary, 
it  may  be  stated  in  general  that  the  symptoms  encountered 
are  those  of  the  disease  or  abnormal  condition  that  causes 
it,  and  not  those  that  are  referable  to  the  kidneys  them- 
selves. 

In  the  severer  forms  of  this  condition,  particularly  when 
due  to  mechanical  irritants  (crystals),  pain  in  the  loins  is 
not  uncommon.  When  due  to  cxposzire  to  cold  and  ivct, 
pain  in  the  loins,  languor,  headache,  neuralgic  pains  in  va- 
rious parts  of  the  body,  and  more  or  less  frequency  of  mic- 
turition are  sometimes  present. 

It  is  probable  that  an  active  hyperemia  or  active  conges- 
tion of  the  kidneys  always  becomes  a  part  of  the  initial 
stage  of  an  acute  nephritis. 

Dropsy  never  exists  as  a  rcstdt  of  an  active  hyperemia  of 
the  kidneys,  even  zvhen  it  is  severe. 


PASSIVE  HYPEREMIA.  289 

Differential  Diagnosis. — From  the  urine  alone  it  is 
often  difficult,  if  not  impossible,  to  distinguish  between  a 
severe  active  hyperemia  (during  its  height)  and  an  acute 
nephritis,  owing  to  the  fact  that  the  albumin  may  be  tem- 
porarily high,  and  the  amount  of  blood  and  number  of 
renal  elements  (casts  and  renal  cells)  abundant.  By  ob- 
serving the  urine  for  a  period  of  a  few  days,  if  a  severe 
hyperemia,  the  amount  of  albumin  and  blood  and  the 
number  of  casts  will  be  found  to  diminish  rapidly.  The 
urine  will  then  have  the  characteristics  of  an  ordinary 
active  hyperemia,  or  the  convalescent  stage  of  this  disturb- 
ance. In  case  the  condition  is  one  of  acute  nephritis  the 
changes  in  the  urine  will  be  more  gradual,  and  the  three 
stages — /".  I'.,  acute,  fatty,  and  convalescent,  are  easily  dis- 
tinguished. The  albumin  will  be  abundant  usually  for  a 
period  of  ten  days  or  two  weeks,  and  the  amount  of  blood 
and  the  number  of  casts  and  renal  cells  will  remain  large. 

A  urine  secreted  just  before  the  fatal  termination  of  a 
chronic  interstitial  nephritis  may  have  all  of  the  characteris- 
tics of  a  mild  active  hyperemia.  The  only  features  of  such  a 
urine  pointing  to  a  chronic  nephritis  are  the  low  quantity 
of  urine  and  the  very  low  total  solids.  A  consideration  of 
the  clinical  history  and  the  symptoms  is  of  the  greatest 
importance  in  differentiating  between  these  two  conditions. 


PASSIVE  HYPEREMIA. 

Passive  hyperemia  of  the  kidneys,  also  termed  chronic 
passive  congestion,  is,  like  active  hyperemia,  not  a  disease 
of  the  kidneys,  but  a  disturbance  that  is  always  secondary 
to  some  obstruction  to  the  venous  circulation.  As  a  result 
of  this,  the  kidneys  are  engorged  with  blood,  and  the 
urine  becomes  modified  to  a  greater  or  less  extent. 

Causes. — (i)  Disease  of  the  heart  accompanied  by  ob- 
struction to  the  flow  of  blood  through  it.  (2)  Liver  disease 
with  obstruction  to  the  passage  of  blood  through  the  as- 
cending vena  cava,  whether  due  to  marked  enlargement  or 
extensive  atrophy  (cirrhosis).  (3)  Ttinwrs  of  the  abdomen, 
including  the  pregnant  uterus,  may  cause  sufficient  obstruc- 
tion to  the  circulation  in  the  kidney  to  cause  a  passive  hy- 
peremia. 

Character  of  the  Urine. — Quantity. — In  uncomplicated 
cases  the  twenty-four-hour  quantity  of  urine  is  diminished, 
19 


290      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

usually  varying  from  400  to  1200  c.c,  but  is  largely  de- 
pendent upon  the  degree  of  obstruction  and  the  character 
of  the  disease  producing  it. 

Color. — Generally  high,  especially  if  due  to  disease  of  the 
liver,  or  a  markedly  uncompensated  heart.  It  may  be 
normal  or  pale  if  due  to  a  long-standing  organic  disease,  or 
following  treatment  by  diuretics. 

Reaction. — Usually  strongly  acid  ;  when  the  urine  is 
dilute  and  of  low  specific  gravity,  the  reaction  is  either  nor- 
mal or  faintly  acid. 

Specific  Gravity. — This  varies  inversely  as  the  quantity, 
and  directly  as  the  metabolism.  If  the  urine  is  high  col- 
ored and  concentrated,  it  will  have  a  specific  gravity  varying 
between  1025  and  1035.  On  the  other  hand,  if  the  urine 
is  pale  and  less  concentrated,  it  will  vary  between  10 12 
and  1020. 

Normal  Solids. — Absolute. — Usually  considerably  di- 
minished, especially  if  the  cause  of  the  disturbance  is 
marked.  Since  there  is  more  or  less  dropsy  accompanying 
the  heart  or  liver  disease,  the  chlorides  and  urea  will  be 
found  absolutely  diminished.  (See  Effect  of  Dropsy  upon 
the  Solids.)  Relative. — Increased,  especially  the  uric  acid. 
In  extreme  cases  accompanied  by  marked  dropsy  the  urea 
and  chlorides  will  be  relatively  diminished. 

Albumin. — This  varies  between  the  slightest  possible  trace 
and  ^  of  I  per  cent,  (except  in  pregnancy,  when  it  may 
exceed  this  quantity).  The  amount  of  albumin  is  generally 
a  very  slight  trace  or  a  trace. 

Sediment. — Frequently  there  is  a  deposit  of  amorphous 
urates.  An  occasional  (or  few)  hyaline  and  finely  granular 
cast  of  small  diameter.  Rarely,  a  renal  cell,  and  voy 
rarely,  a  blood  globule  (blood  is  often  absent).  If  more 
than  a  stray  blood  globule  be  present,  it  is  usually  either 
accidental  or  the  result  of  some  slight  complication.  Fat 
globules  are  not  found  in  the  cells  or  adherent  to  the  casts, 
except  in  case  there  is  some  active  parenchymatous  change 
as  a  complication. 

Not  infrequently  a  passive  hyperemia  is  complicated  by 
an  active  hyperemia,  in  which  case  a  few  blood  globules 
(abnormal)  will  be  found  free  and  adherent  to  casts.  (See 
Differential  Diagnosis.) 

Passive  Hyperemia  of  Pregnancy. — The  urine  of  a  preg- 
nant   woman,  especially   between  the    seventh    and    ninth 


PASSIVE  HYPEREMIA.  291 

months,  will  almost  invariably  show  more  or  less  evidence 
of  a  passive  hyperemia  of  the  kidneys.  Most  of  these 
cases  pass  a  urine  having  the  characteristics  of  passive 
hyperemia  already  described,  except  that  in  pregnancy  it  is 
not  common  to  find  a  highly  concentrated  or  highly  colored 
urine,  but  rather  one  having  a  normal  or  pale  color,  and  a 
normal  or  slightly  low  specific  gravity. 

Occasionally,  the  renal  disturbance  is  severe,  when  the 
albumin  usually  exceeds  -jlg-  of  i  per  cent.,  and  may  go  as 
high  as  i  of  i  per  cent. 

The  renal  casts  in  the  sediment  are  frequently  of  larger 
diameter  than  those  found  in  the  sediment  of  an  ordinary 
passive  hyperemia  due  to  heart  or  liver  disease. 

The  symptoms  encountered  in  passive  hyperemia  are 
those  of  the  disease  or  disturbance  that  causes  the  passive 
congestion  of  the  kidneys  ;  there  are  usually  no  symptoms 
that  are  directly  referable  to  the  kidneys  themselves.  There 
is  generally  dropsy,  mostly  of  the  feet  and  legs  ;  dyspnea  ; 
edema  of  the  lungs,  which  causes  a  hacking  cough  ;  and 
prominence  of  the  veins  of  the  abdomen. 

Differential  Diagnosis. — The  diagnosis  of  an  uncom- 
plicated passive  hyperemia  of  the  kidneys  can  usually  be 
made  from  the  urine  without  a  knowledge  of  the  clinical 
history  or  physical  examination.  If,  however,  the  condi- 
tion is  complicated  in  any  way,  either  by  an  active  hyper- 
emia, acute  nephritis,  or  by  some  chronic  disease  of  the 
kidneys,  the  diagnosis  of  passive  hyperemia  can  not  be 
made  with  certainty  from  the  urine  alone. 

In  the  passiv^e  hyperemia  of  pregnancy  a  rapid  increase  in 
the  quantity  of  albumin  and  an  increase  in  the  number  of 
hyaline  and  finely  granular  casts  in  the  sediment  are  always 
important,  as  these  changes  frequently  serve  as  a  "  danger 
signal  "  to  the  approach  of  puerperal  eclampsia.  It  must  be 
borne  in  mind,  however,  that  puerperal  convulsions  may 
occur  without  there  being  necessarily  any  marked  change 
in  the  quantity  of  albumin  or  the  appearance  of  blood. 
Nevertheless,  this  fact  does  not  lessen  the  importance  of 
carefully  watching  the  urine  for  such  changes  as  may  indi- 
cate the  approach  of  this  serious  complication.  It  is  a  well- 
known  fact  that  chronic  diseases  of  the  kidney  do  not  pre- 
dispose to  the  occurrence  of  puerperal  eclampsia,  even 
though  a  passive  hyperemia  is  superimposed. 

Passive  congestion  of  the  kidneys  is  to  be  distinguished 


292      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

from  a  chronic  interstitial  nephritis  chiefly  by  the  large  quan- 
tity of  urine  and  the  low  absolute  quantity  of  urea  in  the 
latter  disease.  Also  by  the  predominance  in  interstitial  dis- 
ease of  the  quantity  of  urine  passed  at  night  over  that  passed 
during  the  day,  and  by  the  prominent  symptoms  of  intersti- 
tial nephritis — /.  c,  a  full,  hard  pulse,  cardiac  hypertrophy, 
absence  of  dropsy  until  late  in  the  disease,  etc. — all  of  which, 
except  dropsy,  are  absent  in  passive  hyperemia.  In  chronic 
interstitial  nephritis  near  death,  when  the  quantity  of  urine 
has  fallen  to  the  normal  or  below,  it  is  frequently  impossible 
to  distinguish  between  these  two  conditions. 

ACUTE  DIFFUSE  NEPHRITIS   (ACUTE  NEPHRITIS). 

This  condition  consists  of  an  acute  inflammation  or 
degeneration  of  the  kidneys ;  the  pathologic  process  is 
usually  present  in  both  kidneys,  although  it  may  be  entirely 
confined  to  one  of  these  organs.  According  to  Councilman,  ^ 
an  acute  diffuse  nephritis  includes  a  number  of  pathologic 
conditions  :  /.  c. — 

"  (a)  Acute  Degenerative  Nephritis. — In  this  are  in- 
cluded degenerative  lesions  of  the  epithelium,  embracing 
cloudy  swelling,  hyaline,  fatty,  and  dropsical  degeneration, 
and  often  complete  necrosis,  without  lesions  other  than 
degenerative,  in  the  glomeruli  or  in  the  interstitial  tissue. 
This  occurs  chiefly  in  infectious  diseases,  in  jaundice,  in 
anemia,  and  as  the  result  of  the  action  of  certain  poisons. 
The  kidney  is  slightly  swollen  or  unchanged  in  size,  rather 
paler  and  more  opaque  on  section  ;  the  markings  may  be 
obscure  or  more  prominent  than  normal.  There  is  often 
albuminous  exudation  in  the  glomerular  capsules  and  in  the 
tubules. 

(b)  Acute  Glomerular  Nephritis. — The  essential 
changes  consist  in  acute  lesions  in  the  glomeruli.  There 
may  be  acute  proliferation  of  the  endothelium  of  the  vascular 
tufts,  hyaline  and  fibrinous  thrombi  in  the  vessels,  accumula- 
tion of  leucocytes  in  the  vessels,  degeneration  of  the  vessel 
wall,  etc.  These  changes  in  the  vascular  tufts  of  the  glomer- 
ulus can  occur  with  or  without  changes  in  the  capsular  epi- 
thelium. The  changes  in  the  capsular  epithelium  consist  in 
degeneration  and  proliferation.  The  capsular  space  may 
contain  an  albuminous  hemorrhagic  or  fibrinous  exudation. 

^"  Amer.  Journ.  Med.  Sciences,"  July,  1897. 


ACUTE  DIFFUSE  NEPHRITIS.  293 

The  changes  in  the  vascular  tufts  and  in  the  capsule  are  so 
frequently  combined  in  various  degrees  that  they  can  not  be 
separated  into  two  subclasses.  The  glomerular  lesions  are 
accompanied  by  degeneration  of  the  tubular  epithelium, 
necrosis,  and  exfoliation.  Often  there  are  dilatation  of  the 
tubules  and  edema  and  cellular  proliferation  of  the  inter- 
tubular  tissue.  There  may  be  more  or  less  hemorrhage  into 
the  tubules. 

This  affection  occurs  in  infectious  diseases,  notably  in  acute 
endocarditis,  measles,  and  diphtheria,  or  as  an  independent 
affection.  The  kidney  is  usually  increased  in  size.  The 
capsule  easily  strips  off;  the  surface  is  pinkish  and  mottled 
with  points  of  ecchymosis.  On  section  the  cortex  is  wide, 
rather  paler  and  more  opaque,  markings  obscure  ;  glomeruli 
pale,  enlarged,  and  prominent.  Pyramids  often  congested. 
The  tissue  moist  and  pits  on  pressure.  While  these  appear- 
ances are  usually  marked,  lesions  of  the  glomeruli  may  be 
found  with  but  little  macroscopic  change  in  the  kidney. 

(c)  Acute  Hemorrhagic  Nephritis. — The  essential 
change  consists  in  hemorrhage  in  the  tissue  combined  with 
degeneration  of  the  epithelium.  The  hemorrhage  is  chiefly 
found  in  the  capsule  of  the  glomeruli  and  in  the  tubules. 
The  degenerative  lesions  may  be  extensive  and  lead  to 
necrosis  and  exfoliation.  Edema,  hemorrhage,  and  cellular 
infiltration  are  often  found  in  the  intertubular  tissue.  The 
kidney  is  enlarged,  hemorrhages  are  found  in  the  capsule  ; 
the  surface  is  dark  red,  with  numerous  ecchymoses.  On 
section  the  cortex  is  swollen  and  sprinkled  with  dots  and 
streaks  of  ecchymosis. 

(d)  Acute  Interstitial  Nonsuppurative  Nephritis. — 
The  essential  lesion  consists  in  acute  proliferation  of  the  cells 
in  the  intertubular  tissue.  The  proliferation  takes  place 
mainly  from  the  vascular  endothelium.  The  cells  lie  within 
and  without  the  vessels.  They  are  large  and  similar  to  the 
endothelial  cells  of  young  granulation  tissue.  They  are 
found  chiefly  in  the  intermediate  zone  of  the  kidney  between 
the  pyramids  and  the  cortex.  In  the  cortex  they  are  both 
generally  diffused  and  in  areas  chiefly  around  the  glomeruli. 
There  is  more  or  less  degeneration  and  necrosis  of  the 
tubules,  affecting  chiefly  those  in  the  areas  of  cellular  infil- 
tration. Leucocytes  in  small  numbers  may  be  found  in  the 
intertubular  tissue  among  the  other  cells,  in  the  degenerated 
epithelium,  and  in  the  lumen  of  the  tubules.      The  glomeruli 


294      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

are  not  affected.  This  affection  occurs  in  acute  infectious 
diseases,  notably  in  diphtheria  and  scarlet  fever.  The  kidney 
is  large,  pale,  somewhat  mottled  ;  on  section,  moist,  opaque, 
markings  obscure,  and  milky  fluid  can  be  pressed  from  it." 

From  a  clinical  point  of  view  we  are  unable  at  present  to 
distinguish  with  certainty  between  these  four  forms  of  acute 
nephritis,  either  by  the  characteristics  of  the  urine  or  by  a 
consideration  of  the  urine  in  connection  with  the  clinical  his- 
tory and  symptoms.  The  description  that  follows  applies 
to  an  acute  nephritis  as  seen  clinically,  and  is  without  refer- 
ence to  these  different  forms  of  the  disease.  It  is  probable, 
however,  that  the  form  which  Councilman  designates  as 
"  acute  degenerative  nephritis  "  corresponds  to  the  condition 
w^hich  the  author  has  described  as  active  hyperemia. 

Causes. — An  acute  nephritis  may  be  caused  by  any  irri- 
tant or  abnormal  condition,  such  as  causes  an  active  hyper- 
emia (see  Causes  of  Active  Hyperemia) ;  in  fact,  an  active 
hyperemia  from  any  cause  may  end  in  a  true  acute  nephritis. 
Of  the  causes  exposure  to  cold  and  wet  is  probably  the  most 
common.  Toxines,  notably  those  of  diphtheria  and  scarlet 
fever,  are  very  apt  to  cause  acute  nephritis.  Bacterial  in- 
fection is  sometimes  a  cause,  and  when  present,  generally 
produces  the  disease  in  its  most  virulent  form.  In  preg- 
nancy there  may  be  an  acute  nephritis,  which  is  usually  ac- 
companied by  puerperal  convulsions,  and  not  infrequently 
this  complication  proves  fatal. 

An  acute  nephritis  may  be  divided  into  three  stages  :  First 
or  acute,  second  or  fatty,  and  thii^d  or  convalescent  stage. 

First  or  Acute  Stage. — 

Character  of  the  Urine. — Quantity. — Much  diminished 
— usually  200  to  400  c.c.  There  may  be  almost  complete 
anuria,  the  patient  frequently  passing  not  more  than  100  c.c. 
in  forty-eight  hours. 

Color. — Very  smoky  (dark)  or,  in  the  first  day  or  two, 
almost  black  ;  if  much  normal  blood,  a  blood-red  color. 

Reaction. — Usually  acid  ;  sufficient  blood  may  be  pres- 
ent to  give  a  slightly  alkaline  reaction. 

Specific  Gravity. — Generally  high,  although  it  may  be 
low.  If  albumin  be  present  in  large  amount  (and  it  gener- 
ally is  excessive),  it  will  raise  the  specific  gravity  to  1030, 
even  though  the  normal  solids  are  diminished. 

Normal    Solids. — Absolutely,   much    diminished,   espe- 


ACUTE  DIFFUSE  NEPHRITIS.  295 

daily  the  urea  and  chlorine.  (See  Effect  of  Dropsy  on 
Normal  Solids.)  If  the  dropsy  is  increasing,  as  is  the  rule 
during  this  stage,  the  chlorine  may  be  found  absent.  Rela- 
tively, diminished,  especially  the  urea  and  chlorine. 

Albumin. — Generally  }^  to  }4  of  i  per  cent.  It  may 
exceed  this  quantity,  going  as  high  as  i  ^  per  cent.  The 
amount  varies  with  the  severity  of  the  disease  and  the  degree 
of  obstruction  in  the  tubules. 

Sediment. — Abundant  and  of  a  dark-brown  or  choco- 
late color.  It  consists  of  a  large  number  of  abnormal,  and 
perhaps  some  normal,  blood  globules.  Many  brown 
granular  renal  epithelial  cells.  Many  brown  granular, 
epithelial,  blood,  and  fibrinous  casts,  and  perhaps  a  few 
hyaline  and  finely  granular  casts.  A  large  amount  of 
granular  debris  from  the  broken-down  renal  cells  and  blood 
globules.  There  are  usually  numerous  leucocytes,  free,  in 
clumps,  and  adherent  to  the  casts  ;  also  small  caudate  cells 
from  the  superficial  layer  of  the  pelvis,  as  well  as  an  occa- 
sional clump  of  round  cells  from  the  calices  of  the  kidney 
— an  acute  pyelitis. 

The  duration  of  this  stage  is  usually  from  five  to  ten 
days.  The  urine  then  commences  to  show  signs  of  im- 
provement, the  dropsy  begins  to  diminish,  the  absolute 
solids  are  a  little  higher,  the  quantity  of  urine  gradually  in- 
creases, and  fatty  elements  begin  to  appear  or  have  already 
appeared. 

Second  or  Fatty  Stage. — 

Character  of  the  Urine. — Quantity. — This  varies  be- 
tween 800  and  1500  c.c,  according  to  the  amount  of  im- 
provement that  has  taken  place. 

Color. — Still  very  smoky. 

Reaction. — Usually  acid. 

Specific  Gravity. — This  generally  ranges  between  10 15 
and  1020.  It  is  still  influenced  by  the  considerable  amount 
of  albumin  that  is  present. 

Normal  Solids. — Absolutely,  somewhat  diminished,  al- 
though higher  than  in  the  first  stage.  Relatively,  dimin- 
ished. The  urea  and  chlorine  w^ill  be  found  relatively 
higher  as  the  dropsy  diminishes. 

Albumin. — This  varies  between  yi  and  ^  of  i  per  cent. 
As  a  rule,  the  diminution  in  the  quantity  of  albumin  is  in 
inverse  proportion  to  the  increase  in   the   twenty-four-hour 


296      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

quantity  of  urine.      In  the  first  part  of  this  stage  the  quan- 
tity of  albumin  may  exceed  ^  of  i  per  cent. 

Sediment. — This  is  still  abundant  in  quantity,  and  of  a 
brown  color.  The  elements  are  practically  the  same  as  in 
the  acute  stage,  but  with  the  addition  of  fatty  renal  cells, 
fatty  casts,  and  compound  granule  cells.  The  amount  of 
fat  at  this  time  follows  quite  closely  the  degree  of  severity 
of  the  disease  during  the  acute  stage — that  is,  if  there  was  a 
rather  mild  acute  stage,  the  number  of  fatty  elements  and 
the  degree  of  degeneration  will  not  be  extensive  ;  but  if 
there  was  a  severe  acute  stage,  the  quantity  of  fat  will  be 
excessive.  Furthermore,  from  a  single  examination  of  the 
urine  at  this  time,  and  without  a  knowledge  of  the  previous 
history,  it  may  be  impossible  to  determine  whether  we  are 
dealing  with  the  fatty  stage  of  an  acute  nephritis  or  a  sub- 
acute glomerular  nephritis  that  is  complicated  by  an  acute 
process. 

The  evidences  of  a  pyelitis  seen  in  the  acute  stage  will 
probably  be  present  to  a  greater  or  less  extent  in  this  stage, 
although  it  occasionally  happens  that  the  acute  pyelitis 
has  developed  into  a  subacute  or  chronic  pyelitis.  The 
latter  is  shown  by  the  presence  of  a  larger  quantity  of  pus, 
free,  arranged  in  clumps,  and  adherent  to  casts  of  large 
diameter  ;  also  a  large  number  of  small  round  cells,  free 
and  in  the  clumps  of  pus. 

The  duration  of  this  stage  is  about  the  same  as  that  of 
the  first, — viz.,  five  to  ten  days, — providing  there  is  steady 
improvement. 

With  the  favorable  progress  of  the  disease  the  character 
of  the  urine  gradually  changes  still  more,  and  we  have  the 
third  or  convalescent  stage.  The  edema  has  entirely  dis- 
appeared. 

Third  or  Convalescent  Stage. — 

Character  of  the  Urine. — Quantity. — This  generally 
varies  between  i  500  and  3000  c.c.  There  is  usually  a  gradual 
rise  in  the  quantity,  as  high  as  4000  c.c,  where  it  gener- 
ally remains  for  a  few  days  or  even  weeks.  As  the  condi- 
tion approaches  complete  recovery,  the  quantity  falls 
gradually,  and  in  some  cases  there  is  a  sudden  fall  to  about 
the  normal. 

Color. — Usually,  the  urine  has  lost  its  smoky  color  and 
is  pale.      Occasionally,  the   smoky  color  continues,  especi- 


ACUTE  DIFFUSE  NEPHRITIS.  297 

ally  in  the  early  part  of  this  stage,  and  as  long  as  the  urine 
contains  a  large  amount  of  abnormal  blood.  As  the  amount 
of  blood  diminishes,  the  color  becomes  pale. 

Reaction — Faintly  acid. 

Specific  Gravity. — This  varies  as  the  quantity — /.  c,  if 
the  twenty-four-hour  amount  is  between  3000  and  4000  c.c, 
it  will  be  not  far  from  1008  to  1010.  On  the  other  hand, 
if  the  quantity  is  between  1800  and  2500  c.c,  it  will  be  be- 
tween 1012  and  10 1 8. 

Normal  Solids — These  are  absolutely  normal.  They  may 
be  increased  for  a  time,  especially  the  urea  and  chlorides, 
due  to  their  reabsorption  from  the  serous  transudations  and 
their  elimination  in  the  urine.  They  are  relatively  dimin- 
ished, the  degree  of  diminution  being  dependent  upon  the 
dilution  of  the  urine. 

Albumin. — This  is  usually  between  yi  oi  \  per  cent,  and 
a  very  slight  trace,  according  to  the. extent  of  the  convales- 
cence and  the  twenty-four-hour  quantity  of  urine.  The 
larger  the  quantity  of  urine,  the  smaller  the  amount  of  al- 
bumin. The  average  quantity  in  this  stage  will  be  not  far 
from  a  trace. 

Sediment — Generally,  slight  in  quantity  and  colorless, 
although  it  may  still  have  a  brownish  color  if  much  abnor- 
mal blood  be  present.  It  consists  of  numerous  (or  few) 
abnormal  blood  globules.  Few  (or  occasional)  hyaline, 
granular,  and  brown  granular  casts,  and  rarely  a  blood, 
epithelial,  and  fibrinous  cast.  Most  of  the  casts  with 
abnormal  blood  and  a  little  fat  adherent.  Few  renal  cells, 
some  fatty.  Rarely  there  may  be  a  small  fatty  cast.  The 
brown  granular  and  fibrinous  casts  are  the  first  to  disappear. 

If  there  was  a  chronic  pyelitis  in  the  second  stage,  evi- 
dence of  it  will  probably  still  be  found.  As  the  convales- 
cence advances,  the  pyelitis  usually  disappears  rather  sud- 
denly, if  it  has  not  entirely  recovered  during  the  second 
stage. 

The  duration  of  the  convalescent  stage  is  from  one  to 
four  months,  but  not  infrequently  it  lasts  for  a  longer  period, 
even  from  one  to  two  years,  followed  by  complete  recovery. 

In  a  perfectly  favorable  convalescent  stage,  without  com- 
plications, after  the  lapse  of  a  month  or  two,  the  quantity 
of  urine  falls  to  the  normal,  the  albumin  diminishes  to  a  I'ery 
slight  trace  or  the  slightest  possible  trace,  the  quantity  of  blood 
diminishes,  the  brown  granular  and  fibrinous  casts  disap- 


298      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

pear  and  then  the  majority  of  the  fatty  elements.  In  well- 
advanced  convalescence,  only  hyaline  and  granular  casts,  an 
occasional  blood  globule  free  and  adherent  to  some  of  the 
casts,  an  occasional  renal  cell,  and  rarely  a  fatty  renal  cell 
remain.  If  the  urine  is  first  examined  at  this  time  and  with- 
out a  knowledge  of  a  previous  history  of  the  case,  it  is  often 
impossible  to  determine  whether  the  condition  is  one  of 
active  hyperemia  or  a  well-advanced  convalescence  from  an 
acute  nephritis,  for  the  urine  is  the  type  of  one  of  simple 
active  hyperemia.  When  complete  recovery  has  taken 
place,  all  abnormal  elements  disappear  from  the  sediment, 
and  the  urine  is  normal  in  character. 

The  prognosis  in  a  case  of  acute  nephritis  is  usually 
good,  although  there  is  always  a  liability  that  it  may  result 
in  a  chronic  disease  of  the  kidneys.  It  is  certainly  the  ex- 
ception, and  not  the  rule,  for  an  acute  nephritis  to  run  as 
favorable  a  course  as  has  just  been  outlined. 

Exacerbations  (relapses)  are  very  liable  to  occur,  espe- 
cially during  the  convalescent  stage. 

Causes. — Probably  the  most  common  cause  is  exposure 
— a  draft  of  air  on  the  head  and  neck,  too  httle  clothing, 
cold  and  wet  feet,  etc.  Since  the  skin  is  usually  veiy  active 
at  this  time,  any  sudden  exposure  stops  its  action  and  in- 
creases the  congestion  or  inflammation  of  the  kidneys.  Oc- 
casionally, the  ingestion  of  highly  nitrogenous  food  (meats, 
etc.)  is  apparently  an  element  in  causing  an  exacerbation. 
Sometimes  an  exacerbation  occurs  without  a  discernible 
cause,  even  when  the  patient  has  taken  every  precaution. 
The  onset  is  usually  sudden,  and  the  patient  realizes  that 
he  does  not  feel  as  well  as  usual,  having  a  recurrence  of  the 
symptoms  of  the  acute  stage — i.  c,  diminished  quantity  of 
urine,  frequent  micturition,  and  generally  some  headache  and 
pain  in  the  back.  There  is  usually  more  pallor  than  before 
the  attack,  and  often  swelling  of  the  face  and  extremities. 

Cliaractcr  of  the  Urine. — The  urine  of  an  exacerbation 
is  characterized  (i)  by  a  sudden  fall  in  the  quantity,  (2)  a 
blood-red  color,  and  (3)  the  presence  in  the  sediment  of  a 
large  quantity  of  normal  blood.  It  may  be  either  mild  or 
severe,  and  the  severity  of  the  attack  governs  the  extent  to 
which  the  quantity  of  urine  is  diminished,  and  the  amount  of 
normal  blood  found  ;  in  other  words,  if  severe,  the  quantity 
of  urine  is  greatly  reduced  and  the  amount  of  normal  blood 
large  ;  if  mild,  a  moderately  diminished  quantity  and  com- 


ACUTE  DIFFUSE  NEPHRITIS.  299 

paratively  little  blood.  The  quantity  of  albumin  increases 
and  the  normal  solids  diminish  according  to  the  severity. 
The  blood,  epithelial,  and  fibrinous  casts  are  again  present  in 
moderately  large  numbers.  In  the  course  of  two  or  three 
days,  possibly  a  week  or  ten  days,  the  urine  again  increases 
and  the  normal  blood  disappears,  although  the  latter  may 
continue  in  small  amount  (not  sufficient  to  give  the  urine  a 
bloody  color)  for  weeks.  Following  the  disappearance  of 
the  greater  part  of  the  normal  blood,  the  urine  generally 
contains  a  larger  quantity  of  abnormal  blood  than  before 
the  exacerbation,  hence  a  smoky  color  again  for  a  few  days. 
After  a  short  time  has  elapsed  the  urine  again  presents  the 
characteristics  of  the  third,  or  convalescent,  stage  of  an  acute 
nephritis. 

Any  number  of  exacerbations  may  occur,  the  average 
being  from  one  to  four,  and  the  larger  the  number,  the  more 
prolonged  the  convalescence.  Likewise,  the  greater  the 
number  of  exacerbations,  the  more  extensive  the  pathologic 
changes  in  the  kidney,  and  hence  the  more  unfavorable 
the  prognosis,  since  the  acute  nephritis  may  end  in  a  chronic 
disease  of  the  kidneys.  An  unfavorable  prognosis  is  not 
necessarily  warranted,  however,  as  cases  of  acute  nephritis 
accompanied  by  frequent  exacerbations  have  recovered  after 
a  lapse  of  two  years. 

Symptoms  of  uremia  may  appear  at  the  time  of  a  severe 
exacerbation  because  of  the  interference  with  the  elimination 
of  the  toxic  material  from  the  body  ;  but,  fortunately,  this 
complication  is  only  rarely  seen. 

Prominent  Symptoms. — The  onset  of  an  acute  nephritis 
is  usually  very  rapid  and,  like  other  acute  processes,  is  fre- 
quently ushered  in  by  a  chill.  There  is  usually  rapid  pallor, 
swelling  of  the  lower  eyelids  and  face,  also  edema  of  the  legs, 
and  often  general  dropsy  ;  intense  headache,  thirst,  nausea, 
and  often  vomiting ;  pain  in  the  back  and  limbs,  and 
frequency  of  micturition.  Because  of  the  last-mentioned 
symptom  the  patient  often  has  the  firm  impression  that  he  is 
passing  a  large  quantity  of  urine,  but  when  the  total 
quantity  is  measured,  it  will  be  found  to  be  abnormally 
diminished.  There  is  usually  at  first  some  elevation  of  tem- 
perature, also  a  high  tension  pulse.  Acute  uremic  symp- 
toms are  not  uncommon,  the  most  prominent  of  which  are 
nausea  and  vomiting,  stupor,  and  sometimes  convulsions. 
Acute  visual  disturbances  are  occasionally  seen. 


300      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

Differential  Diagnosis. — The  distinction  between  a 
severe  active  J'.ypercDiia  and  a  mild  acute  nephritis  is,  in  some 
instances,  not  easily  deduced  from  the  urine  alone.  How- 
ever, the  history  of  a  sudden  onset  and  the  prominent  symp- 
tom of  edema, — swelling  of  the  face  and  legs, — together  with 
the  chief  characteristics  of  the  urine — viz.,  the  persistence 
of  a  considerable  amount  of  albumin,  considerable  blood, 
and  numerous  casts — will  serve  to  distinguish  an  acute 
nephritis  from  a  severe  form  of  active  hyperemia. 

The  urine  of  the  second  stage  of  acute  nephritis  may  not 
differ  materially  from  one  of  subacute  glomendar  nephritis 
{active  stage)  complicated  by  an  acute  process.  In  the  latter 
condition  the  albumin  is  usually  present  in  larger  amounts, 
and  the  total  quantity  of  urea  is  gencrall}^  much  lower  than 
in  the  former  disease.  In  an  acute  nephritis  the  clinical 
symptoms  will  show  that  the  condition  is  gradually  improv- 
ing, while  in  a  case  of  a  complicated  subacute  glomerular 
nephritis  the  patient  is  at  his  worst.  In  doubtful  cases, 
however,  the  urine  should  be  carefully  watched  for  several 
days  ;  if  an  acute  nephritis,  the  third  or  convalescent  stage 
will  appear  ;  if  a  subacute  glomerular  nephritis  complicated 
by  an  acute  process,  the  acute  complication  will  gradually 
subside,  leaving  the  disease  in  its  uncomplicated  form  ;  or 
the  patient  may  have  S}'mptoms  of  uremia  and  succumb  to 
the  disease. 

The  urine  of  the  coiivalescent  stage  of  an  acute  nepJiritis 
should  not  be  mistaken  for  the  urine  of  chronic  interstitial 
or  cJironic  diffuse  nepJiritis.  The  acute  histor>',  the  charac- 
teristic first  and  second  stages  of  an  acute  nephritis,  the 
presence  of  blood  in  the  sediment,  and  the  normal  total  solids 
will  serve  to  distinguish  an  acute  from  a  chronic  form  of  renal 
disease. 

SUBACUTE  GLOMERULAR  NEPHRITIS. 

Subacute  glomerular  nephritis,  also  termed  "  chronic  par- 
enchymatous nephritis,"  "  fatty  degeneration  of  the  kid- 
neys," and  "  chronic  diffuse  nephritis  of  the  parenchymatous 
type,"  is  a  disease  characterized  by  marked  degenerations 
of  the  glomeruli  as  well  as  of  the  epithelial  lining  of  the 
renal  tubules. 

The  essential  lesions  are  in  the  glomeruli.  They  consist 
in  swelling  and  nuclear  increase  in  the  vascular  tufts  and 
obliteration  of  the  vessels  by  hyaline  degeneration,  both  of 


SUBACUTE  GLOMERULAR  NEPHRITIS.  301 

the  cells  and  the  vascular  walls.  These  changes  in  the  tufts 
are  often  combined  with  proliferation  and  desquamation  of 
the  capsular  epithelium  with  connective-tissue  ingrowth. 
There  is  extensive  degeneration,  necrosis,  and  desquamation 
of  the  tubular  epithelium.  The  intertubular  tissue  is  the 
seat  of  edema  and  connective-tissue  formation.  The  kidney 
is  enlarged,  and  the  capsules  may  cling  slightly  to  the  sur- 
face, which  is  pale  and  slightly  mottled.  On  section,  the 
cortex  is  increased  in  width,  pale,  opaque,  markings  obscure, 
glomeruli  pale,  and  its  consistency  is  increased  (Council- 
man). 

Causes. — This  disease  is  sometimes  the  result  of  a  pre- 
vious acute  nephritis,  during  the  course  of  which  frequent 
exacerbations  hav^e  occurred,  and  when  the  convalescence 
has  been  extended  over  a  long  period  (years).  It  is,  per- 
haps, more  common  for  the  disease  to  accompany  chronic 
wasting  diseases,  such  as  phthisis,  syphilis,  and  chronic 
suppurative  bone  diseases  ;  also  in  cases  of  prolonged 
malaria.  When  the  disease  is  an  accompaniment  of  these 
conditions,  the  changes  in  the  kidney  are  gradual,  and  the 
disease  appears  to  be  chronic  from  the  beginning.  The  rea- 
son for  a  subacute  glomerular  nephritis  under  these  circum- 
stances is  not  known. 

The  disease  can  be  conveniently  divided  into  two  stages — 
/.  c,  active  and  inactive  stages. 


ACTIVE  STAGE. 

This  stage  is  seen  at  the  time  when  the  patient  is  at  his 
worst.  The  urine  is  concentrated  and  highly  characteristic, 
and  there  is  marked  dropsy. 

Character  of  the  Urine. — Quantity. — Very  small,  vary- 
ing from  200  to  800  c.c,  the  average  being  not  far  from 
400  c.c. 

Color. — High,  like  that  of  a  fever  urine,  and  often  turbid 
because  of  the  presence  of  amorphous  urates.  In  case  of 
a  recent  acute  exacerbation,  the  color  will  be  bloody. 

Reaction, — Usually  strong  acid. 

Specific  Gravity. — High — 1026  or  1028,  and  often  as 
high  as  1030  or  1035. 

Normal  Solids. — Absolutely,  much  diminished,  especially 
the  urea  and  chlorides,  which  are  low  because  of  the  very 
extensive   and  increasing  dropsy.      The  chlorides  may  be 


302      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

nearly  absent.  Relatively,  the  uric  acid  and  the  urea  are  in- 
creased, unless  the  disease  has  been  going  on  for  a  long 
time,  in  which  case  the  urea  will  be  relatively  diminished. 
The  chlorides  are  much  diminished  or  nearly  absent. 

Albwnin. — In  this  form  of  kidney  disease,  and  especially 
in  this  stage,  the  quantity  of  albumin  is  the  largest  ever  found 
in  the  urine.  It  varies  between  y^,  of  i  and  3  or  4  per  cent, 
by  weight,  but  the  average  quantity  is  usually  from  ^  of  i  to 
I  per  cent.  The  maximum  amount  ev^er  reported  was  as  high 
as  5  per  cent.  Upon  performing  the  heat  test  for  albumin 
it  is  not  very  uncommon  to  find  that  the  urine  completely 
solidifies,  in  which  case  the  quantity  of  albumin  exceeds  2 
per  cent.  The  average  quantity  in  this  stage  is  between  ^ 
of  I  and  I  per  cent.,  usually  nearer  the  latter  figure. 

Sediuteiit. — If  a  deposit  of  amorphous  urates  is  present, 
the  sediment  will  be  abundant  and  usually  of  a  pink  or  red- 
dish-brown color.  If  there  is  not  a  deposit  of  urates,  the 
amount  of  sediment  will  be  "  considerable  "  and  practically 
colorless.  If  the  disease  be  complicated  by  an  acute  pro- 
cess, normal  blood  may  be  present  in  sufficient  quantity  to 
color  the  urine  and  sediment  red.  The  sediment  consists  of 
many  hyaline,  granular,  and  fatty  casts,  some  of  which  have 
fatty  renal  and  compound  granule  cells  adherent ;  numer- 
ous//r^'  fatty  renal  and  compound  granule  cells.  Crystals 
of  the  fatty  acids  are  often  seen  projecting  from  the  fatty 
renal  and  compound  granule  cells,  and  the  fatty  casts. 
Cholesterin  cr}^stals  are  occasionally  seen,  but  usually  only 
in  the  late  stages  of  the  disease.  If  the  disease  is  well  ad- 
vanced, waxy  casts  may  be  seen  in  the  sediment.  When 
present,  they  are  of  bad  omen.  In  an  uncomplicated  case  the 
sediment  is  free  from  blood  and  renal  blood  elements.  As  a 
matter  of  fact,  chronic  diseases  of  the  kidneys  are  usually 
more  or  less  complicated  by  either  a  mild  or  severe  acute  pro- 
cess, so  that  usually  an  occasional  (or  numerous)  blood 
globule  will  be  found.  If  there  is  very  much  blood  present, 
a  few  leucocytes  are  often  found  free  and  adherent  to  some 
of  the  casts. 

With  the  improvement  that  usually  follows  rest  in  bed, 
a  milk  diet,  and  mild  diuretic  treatment,  providing  the  dis- 
ease is  not  near  its  termination,  there  is  a  distinct  change  in 
the  character  of  the  urine.  The  dropsical  effusions  have 
diminished,  the  edema  of  the  extremities  has  largely  disap- 
peared, although  usually  not  entirely,  and  the  process  in  the 


SUBACUTE  GLOMERULAR  NEPHRITIS.  303 

kidneys  appears  to  be  quiescent.     Then  we  have  the  inac- 
tive stage  of  the  disease. 

INACTIVE  STAGE. 

Character  of  the  Urine. — Quantity.— Usually,  from 
800  to  1200  c.c.  It  may  exceed  the  normal  quantity  for  a 
day  or  two  at  the  time  the  edema  is  being  absorbed,  but 
it  soon  falls  to  about  1200  c.c. 

Color. — The  color  is  pale  and  not  infrequently  the  urine 
has  a  greenish  tint. 

Reaction. — Generally,  acid. 

Specific  Gravity. — This  varies  as  the  twenty-four-hour 
quantity,  but  in  the  early  part  of  the  disease  it  will  gen- 
erally vary  between  10 10  and  10 15. 

Normal  Solids. — They  are  both  absohitely  and  relative- 
ly diminished.  The  solids  may  be  absolutely  somewhat 
higher  than  in  the  active  stage,  especially  at  the  time  of  the 
greatest  absorption  of  the  edema,  but  the  increase  is  usually 
slight. 

Albumin. — The  quantity  of  albumin  is  smaller  than  in 
the  active  stage,  but  it  is  still  present  in  large  amount,  gen- 
erally from  %  to  yi  of  I  per  cent.  Occasionally,  it  is  a 
little  less  than  y^  of  i  per  cent.,  particularly  if  the  twenty- 
four-hour  quantity  of  urine  is  about  i  500  c.c. 

Sediment. — This  is  "considerable"  in  quantity,  and 
colorless.  A  deposit  of  amorphous  urates  is  usually  not 
present.  It  consists  of  the  same  elements  that  were  found 
in  the  active  stage,  but  they  are  less  in  number  :  numerous 
hyaline,  granular,  and  fatty  casts,  fatty  renal  and  compound 
granule  cells.  If  waxy  casts  were  present  in  the  active 
stage,  they  will  be  found  at  this  time,  although  fewer  in 
number.  Crystals  of  the  fatty  acids  and  cholesterin  will 
also  be  found  if  the)^  were  present  in  the  active  stage. 

ATROPHIC  STAGE. 

This  stage  is  only  very  rarely  seen,  since  death  usually 
occurs  before  atrophy  of  the  kidneys  has  taken  place.  The 
kidneys  become  very  small,  have  a  yellow  color,  consist 
principally  of  fat,  and  there  is  a  marked  increase  in  the  con- 
nective tissue. 

Character  of  the  Urine. — The  quantity  of  urine  is  usually 
not  far  from  the  normal,  and  it  may  be  slightly  increased. 


304      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

The  specific  gravity  and  the  normal  solids  are  very  low  ;  the 
quantity  of  albumin  falls  to  about  y^  of  i  per  cent,  or  less  ; 
and  the  sediment  consists  of  practically  the  same  elements 
as  in  the  inactive  stage  of  the  disease,  except  a  smaller 
number  of  fatty  elements  and  a  larger  proportion  of  waxy 
casts. 

A  subacute  glomerular  nephritis  is  characterized  by  fre- 
quent alternations  of  the  active  and  passive  stages,  without 
there  being  necessarily  a  true  acute  exacerbation.  But 
acute  exacerbations  are  as  likely  to  occur  in  this  disease 
as  in  an  acute  diffuse  nephritis.  When  present,  the  urine 
has  the  additional  elements  of  the  acute  disease,  together 
with  the  normal  blood  and  renal  blood  elements — blood- 
casts,  etc. 

Prominent  Symptoms. — The  patient  usually  suffers  from 
indigestion  (early  symptom),  often  attended  with  vomiting  ; 
almost  constant  headache,  which  gradually  increases  in  in- 
tensity from  month  to  month  ;  marked  pallor  ("  pasty")  and, 
usually,  swelling  of  the  face  ;  and  invariably  marked  edema 
of  the  extremities,  which  finally  extends  and  increases  to  a 
condition  of  extreme  general  dropsy  (ascites,  pleuritic  effu- 
sion, etc.).  There  is  frequency  of  micturition,  but  a  small 
quantity  of  urine  is  passed.  Palpitation  and  dyspnea  on  ex- 
ertion are  often  present  to  a  marked  degree.  The  disease 
is  characterized  by  periods  of  activity  in  which  the  edema 
is  increased,  the  quantity  of  urine  is  very  small,  and 
there  are  uremic  symptoms.  It  is  also  characterized  by 
quiescent  periods,  in  which  the  patient  improves,  the  edema 
diminishes,  and  the  quantity  of  urine  increases,  although 
generally  not  above  the  normal  except  for  a  day  or  two. 

The  duration  of  the  disease  is  usually  from  two  to  five 
years,  but  this  depends  upon  the  care  of  the  patient  and 
the  hygienic  surroundings.  If  the  circumstances  are  such 
that  he  can  have  the  very  best  care,  life  may  be  pro- 
longed a  year  or  two  longer ;  on  the  other  hand,  an 
early  end  is  often  the  fate  of  such  cases  among  the  poorer 
classes. 

The  prognosis  is  invariably  unfavorable.  So  far  as  is 
known,  recovery  never  takes  place  after  the  disease  has  be- 
come well  established.  Death  may  result  from  uremia  or, 
as  is  not  infrequent,  from  some  secondary  acute  disease, 
such  as  pneumonia,  erysipelas,  diphtheria,  etc.  The  low 
physical  state  of  the  patient  renders  him  very  susceptible 


CHRONIC  INTERSTITIAL  NEPHRITIS.  305 

to  other  diseases,  especially  those  of  an  acute   infectious 
nature. 

Differential  Diagnosis. — The  diagnosis  of  a  subacute 
glomerular  nephritis  from  the  urine  alone  is  generally  not 
difficult,  providing  the  condition  is  uncomplicated.  In  case 
the  disease  is  complicated  by  an  acute  process  it  can  not  be 
readily  distinguished  from  the  second  stage  of  an  acute 
nephritis.  Under  these  circumstances  the  history  of  the 
case  should  be  considered,  and  the  character  of  the  urine 
should  be  carefully  watched  for  several  days.  If  a  compli- 
cated subacute  nephritis,  the  acute  process  will  generally 
subside  in  the  course  of  from  two  to  three  weeks,  when  the 
urine  will  have  the  characteristics  of  an  uncomplicated  sub- 
acute nephritis.  The  edema  that  was  extreme  at  first 
usually  continues  after  the  acute  process  has  subsided — viz., 
after  the  blood  has  entirely  disappeared.  On  the  other 
hand,  if  the  disease  is  an  acute  nephritis  passing  through  the 
second  stage,  the  third  or  convalescent  stage  will  soon  ap- 
pear, the  edema  will  entirely  subside,  and  the  patient  will 
gradually  improve  until  there  is  complete  convalescence. 

CHRONIC  INTERSTITIAL  NEPHRITIS. 

This  condition  has  been  variously  termed  chronic  neph- 
ritis, chronic  diffuse  nephritis  of  the  interstitial  type,  sclerotic 
kidney,  gouty  kidney,  small  gramdar  kidney,  chronic  diffuse 
nephritis  without  exudation,  etc.  It  is  a  chronic  disease  of 
the  kidneys,  which  is  characterized  chiefly  by  an  increase  in 
the  connective  tissue  of  those  organs.  The  disease  develops 
very  slowly  and  insidiously,  usually  having  been  in  prog- 
ress for  years  before  it  is  recognized,  and  then  often  only 
accidentally  discovered  by  the  physician  who  is  consulted 
for  the  relief  of  headaches  or  some  annoying  stomach  diffi- 
culty ;  or  perhaps  it  is  first  encountered  by  the  life  insur- 
ance examiner  or  oculist. 

According  to  Councilman,  some  of  the  pathologic  pro- 
cesses found  in  chronic  interstitial  nephritis,  such  as  chroidc 
arteriosclerotic  ncpJiritis,  and  chronic  degenerative  and  inter- 
stitial nephritis  really  belong  under  the  heading  of  chronic 
diffuse  nephritis. 

In  chronic  arteriosclerotic  nephritis  the  essential  lesions 
occur  in  the  arteries,  and  consist  in  those  changes  known 
as  arterioscleroses.  There  is  degeneration  of  the  epi- 
20 


306      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

thelium  of  the  tubules,  with  more  or  less  complete  de- 
struction. The  degeneration  takes  place  slowly,  and  at 
any  given  time  sections  may  show  only  a  slight  degree. 
Atrophic  changes  in  the  epithelium  are  common.  The 
lesions  may  affect  almost  equally  all  parts  of  the  kidney,  or 
appear  in  areas  corresponding  to  the  vascular  territories  of 
those  arteries  that  are  most  affected.  There  is  a  general 
increase  in  the  connective  tissue,  though  large  areas  of 
tubules  may  be  found  with  no  increased  tissue  between 
them.  This  condition  of  the  kidney  is  found  accompany- 
ing a  general  arteriosclerosis  affecting  all  the  arteries  of  the 
body,  or  the  vascular  lesions  may  be  most  marked  in  the 
renal  arteries.  The  kidney  varies  in  size  ;  it  may  be 
slightly  larger  or  of  normal  size,  but  is  usually  very  much 
smaller  than  normal.  The  capsule  may  or  may  not  be 
adherent.  The  surface  is  more  or  less  irregular  and  granu- 
lar ;  the  color  is  red  and  often  cyanotic.  On  section,  the 
cortex  may  be  much  diminished  in  size,  of  a  dark-red 
color,  the  markings  obscure,  and  the  glomeruli  injected  ; 
the  arteries  in  the  intermediate  portion  are  evident,  and  often 
project  above  the  cut  surface.  The  pyramids  show  venous 
congestion  ;  the  consistency  of  the  kidney  is  greatly  in- 
creased. Most  of  the  cases  of  contracted  kidney  belong  to 
this  class. 

To  the  class  of  cJironic  degenerative  and  interstitial  neph- 
ritis belong  those  cases  of  contracted  granular  kidney  that 
occur  without  primary  arterial  lesions.  It  is  difficult  to  give 
a  name  to  the  condition,  for  there  is  no  single  change 
that  predominates.  Degeneration,  atrophy,  and  destruc- 
tion of  the  epithelium  in  various  degrees  are  found.  There 
is  a  general  increase  in  connective  tissue  more  diffuse  than 
in  the  arteriosclerotic  nephritis,  but  not  so  diffuse  as  in  the 
chronic  glomerular  form.  The  increase  in  the  connective 
tissue  is  most  intense  where  the  degeneration  of  the  epithe- 
lium is  most  marked.  Lines  of  connective  tissue  extend  to 
the  surface,  and  by  their  contraction  produce  depressions. 
Very  minor  degrees  of  change,  which  may  consist  in  small 
areas  of  cellular  infiltration  with  hyperplasia  of  the  connec- 
tive tissue  extending  down  from  the  capsule,  are  very  com- 
monly found.  The  essential  lesion  seems  to  be  a  slow 
degeneration  of  the  epithelium,  followed  by  connective-tis- 
sue hyperplasia.  The  microscopic  appearances  of  the  kid- 
ney vary  extremely,  following  the  different  degrees  of  the 


CHRONIC  INTERSTITIAL  NEPHRITIS.  307 

lesions.      The  gross  and  microscopic  condition  may  be  com- 
plicated by  lesions  of  another  character  (Councilman). 

Causes. — There  are  three  toxic  agents  that  are  probably 
causes  of  this  disease  : 

1.  Lead. — Chronic  lead-poisoning  is  usually  met  with  in 
type-setters,  painters,  those  handling  lead,  and  others  ex- 
posed to  its  influence.  The  damage  to  the  kidneys  is 
apparently  due  to  the  constant  elimination  of  the  lead,  which 
acts  as  a  chemic  irritant.  The  connective -tissue  changes 
do  not  usually  appear  until  after  years  of  almost  constant 
poisoning. 

2.  Alcohol. — Those  persons  who  are  addicted  to  the 
moderate  use  of  alcohol,  especially  if  continued  for  years, 
may  have  a  chronic  interstitial  nephritis,  which  may  lead  to 
their  death  or  be  an  accompaniment  of  some  other  acute  or 
chronic  disease  that  proves  fatal. 

3.  Uric  Acid. — The  gouty  individual  is  often  the  victim 
of  this  disease — the  so-called  "  gouty  kidney."  The  man- 
ner in  which  uric  acid  produces  a  chronic  interstitial  nephri- 
tis can  not  be  well  explained  unless  we  assume  that  it  is  the 
result  of  the  constant  irritation  set  up  by  the  elimination  of 
excessive  amounts  of  uric  acid  and  other  products  of 
diminished  metabolism. 

Arsenic. — Chronic  arsenic-poisoning  probably  leads  to 
this  form  of  disease,  especially  in  those  persons  who  have 
been  exposed  to  the  influence  of  the  substance  for  a  long 
period  of  years. 

Syphilis  and  chronic  malaria  are  also  considered 
causes  of  this  disease.  It  is  certain  that  these  conditions 
are  often  accompanied  by  a  chronic  interstitial  nephritis,  but 
not  invariably.  It  is  probable  that  any  long-continued  irri- 
tation of  the  kidneys  gradually  results  in  renal  changes 
that  finally  terminate  in  a  chronic  interstitial  nephritis. 

Arteriosclerosis. — There  can  be  no  doubt  that  this  dis- 
ease of  the  blood-vessels  results  in  those  changes  that 
characterize  this  form  of  kidney  disease.  It  is  common  in 
middle-life,  and,  as  before  stated,  most  of  the  cases  of  con- 
tracted kidney  belong  to  this  class. 

Chronic  interstitial  nephritis  can  be  divided,  clinically, 
into  three  stages  according  to  the  degree  to  which  the  urine 
becomes  modified  from  the  normal  and  the  extent  of  the 
renal  changes  :  first  or  early  stage,  second  or  advanced 
stage,  and  third  of  late  stage. 


808      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

FIRST  OR  EARLY  STAGE. 

This  stage  is  seen  at  the  time  when  the  individual  is 
capable  of  attending  to  business  and,  with  the  exception  of 
headaches  and  frequent  attacks  of  indigestion,  enjoys  a  fair 
degree  of  health.  There  may  not  be  any  noticeable  fre- 
quency of  micturition  at  this  time,  although  the  patient  will 
probably  find  it  necessary  to  urinate  once  or  twice  during 
the  night. 

Character  of  the  Urine. — Quantity. — This  is  a  very 
important  element  in  the  diagnosis.  It  is  moderately  in- 
creased above  the  normal  at  this  time — usually,  between 
1500  and  2000  c.c.  Frequently,  the  quantity  of  urine 
passed  at  night  exceeds  that  passed  during  the  day  ;  this 
is  much  more  marked  during  the  advanced  stage  of  the 
disease. 

Color. — Normal  or  slightly  pale. 

Reaction. — Acid. 

Specific  Gravity. — This  varies  inversely  as  the  quantity 
of  urine,  but  will  usually  be  found  to  vary  between  1012 
and  1018. 

Coloring-matters. — All  somewhat  diminished  except 
the  indoxyl,  which  is  generally  increased. 

Normal  Solids. — The  absolute  solids  are  somewhat 
diminished,  although  not  markedly.  The  total  quantity  of 
urea  eliminated  by  an  average-sized  adult  will  be  about  nor- 
mal, or  it  may  be  higher  than  normal,  especially  if  the  indi- 
vidual is  having  a  liberal  nitrogenous  diet.  Relatively,  they 
are  nearly  normal  or  somewhat  diminished,  depending  on  the 
dilution  of  the  urine.  The  percentage  of  urea  will  probably 
be  found  to  be  not  far  from  1.5  per  cent. 

Albumin. — This  varies  between  the  slightest  possible  trace 
and  a  trace.  It  is  at  this  time  that  the  presence  of  albumin 
is  sometimes  overlooked,  because  of  the  failure  to  detect 
the  slightest  possible  traces.  (See  Detection  of  Albumin.) 
The  author's  experience  leads  him  to  believe  that  albumin  is 
ahvays  present  in  the  urine  of  chronic  interstitial  nephritis, 
even  in  the  early  stages. 

Sediment. — This  is  usually  very  slight  in  quantity  and 
requires  very  careful  sedimentation  in  order  to  be  able  to 
obtain  a  satisfactory  preparation  for  examination.  Often- 
times it  is  necessary  to  centrifugalize  the  urine  in  order  to 
obtain  the  best  results  from  the  microscopic  examination. 


CHRONIC  INTERSTITIAL  NEPHRITIS. 


309 


It  Will  be  found  to  consist  of  an  occasional  hyaline  and  finely 
granular  cast.  No  excess  of  renal  cells  and,  unless  com- 
plicated, no  blood  or  fat  are  present. 

In  this  stage  the  diagnosis  of  chronic  interstitial  nephritis 
from  the  urine  alone  is  usually  extremely  difficult,  but  when 
combined  with  the  clinical  history  and  ph)-sical  examination 
It  becomes  less  difficult,  although  often  doubtful  until  the 
case  has  been  carefully  watched  for  some  months. 

SECOND  OR  ADVANCED  STAGE. 
The  patient  at  this  time  usually  finds  it  necessary  to  dis- 
continue business,  because  of  lack  of  strength,  habitual 
headache,  more  or  less  marked  gastric  disturbance,  and 
perhaps  other  more  serious  symptoms  ;  in  other  words,  the 
disease  is  at  its  height,  and  the  patient  requires  almost  con- 
stant attention. 

Character  of  the  Urine.— Quantity.— This  gradually 
but  steadily  increases    from    2000   to    3000   or  4000   c.c. 
Rarel}',  it  may  go  as  high  as  6000  c.c.  in  twenty -four  hours. 
Color. — Pale  and  sometimes  almost  colorless. 
Reaction  — Faintly  acid. 

Specific  Gravity. — This  has  fallen  from  1012  or  1015 
to  1 010  or  lower.  . 

Normal  Solids.— ^/7.y^V///^/j/,  much  diminished.  Occa- 
sionally, if  the  disease  is  not  very  far  advanced  and  the 
patient  is  having  the  best  of  care  and  can  take  a  moderately 
nitrogenous  diet,  the  urea  may  be  nearly  or  quite  normal, 
but  this  does  not  continue  for  a  very  long  time.  Relatively, 
much  diminished. 

Coloring-matters.— These  are  all  diminished,  except 
the  indoxyl,  which  is  often  normal  or  increased. 

Albumin. — This  has  increased,  and  usually  varies  be- 
tween a  trace  and  yi  of  i  per  cent.  It  may  rarely  reach 
y^  of  I  per  cent. 

Sediment. — This  is  much  the  same  as  in  the  early  stage, 
except  that  the  casts  are  more  numerous  and  usually  more 
granular.  The  renal  cells,  which  are  only  few  in  number, 
will  be  found  to  be  quite  granular.  Oftentimes  the  abnor- 
mally formed  renal  elements  are  found  with  some  difficulty, 
since  the  amount  of  sediment  is  so  slight.  As  in  the  early 
stage,  the  urine  may  require  centrifugalization  in  order  to  ob- 
tain a  satisfactory  sediment  for  examination. 


310      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

THIRD  OR  LATE  STAGE. 

This  is  at  a  time  when  the  disease  has  advanced  to  a  late 
stage,  and  the  patient  is  more  or  less  uremic — /.  e.,  suffering 
from  intense  headache,  nausea,  vomiting,  and  often  convul- 
sions. General  weakness  is  marked.  Dyspnea  is  often  a 
prominent  symptom.  There  is  considerable  vertigo  and 
disturbance  of  vision — the  so-called  albinnimiric  retinitis. 
There  may  be  some  edema  of  the  feet  at  this  time,  due  to 
an  uncompensated  heart. 

Character  of  the  Urine. — Quantity. — This  has  gradu- 
ally fallen  from  the  large  quantity  to  about  1500  c.c.  The 
quantity  of  urine  passed  at  night  is  usually  greater  than  that 
passed  during  the  day. 

Color. — Veiy  pale  (watery). 

Reaction. — Faintly  acid. 

Specific  Gravity. — Usually  between  1005  and  loio  ; 
even  when  the  twenty-four-hour  quantity  of  urine  is  much 
below  the  normal — e.g.,  with  a  quantity  of  500  c.c.  the 
specific  gravity  may  be  as  low  as  1005. 

Normal  Solids. — Both  absolutely  and  relatively  much 
diminished. 

Albumin. — Usually,  a  distinct  trace  ;  rarely,  the.  slightest 
possible  trace.  It  may,  on  the  other  hand,  reach  as  high  as 
]^  of  I  per  cent. 

Sediment. — This  is  still  slight  in  quantity,  and  consists 
of  numerous  (or  many)  hyaline,  finely  and  coarsely  granu- 
lar, and  a  few  waxy  casts.  Most  of  the  renal  cells  will  be 
found  to  be  very  granular.  No  fat  nor  blood  unless  com- 
plicated. Often  in  the  late  stage  a  few  abnormal  blood 
globules  will  be  found.  It,  therefore,  may  be  difficult  from 
the  urine  alone  and  without  a  previous  knowledge  of  the 
case  to  make  a  diagnosis  of  a  primary  renal  disease,  espe- 
cially if  the  quantity  of  urine  is  small  and  the  waxy  casts 
are  stained  by  the  blood  so  as  to  resemble  fibrinous  casts. 
The  blood  may  be  due  to  a  slight  acute  exacerbation,  or  it 
may  be  the  result  of  either  a  circumscribed  acute  nephritis  or 
a  more  or  less  general  active  hyperemia.  If  the  disease  is 
the  result  of  some  active  irritant  (lead  or  arsenic),  blood  may 
be  found  in  the  sediment  in  all  stages  of  the  disease. 

Prominent  Symptoms. — Owing  to  the  latency  of  the 
disease,  symptoms  are  frequently  not  noticed  until  the 
occurrence   of  one   of  the   serious  or    fatal    complications. 


CHRONIC  INTERSTITIAL  NErHRITIS.  311 

Even  an  advanced  grade  of  chronic  interstitial  nephritis  may 
be  compatible  with  great  mental  and  bodily  activity.  There 
may  have  been  no  symptoms  whatever  to  suggest  to  the 
patient  the  existence  of  a  serious  disease.  In  other  cases 
the  general  health  is  greatly  disturbed.  The  patient  com- 
plains of  lassitude,  sleeplessness,  has  to  arise  two  or  three 
times  at  night  to  micturate,  the  digestion  is  disordered,  and 
there  are  complaints  of  headache,  failing  vision,  and  shortness 
of  breath  on  exertion.  The  pulse  is  usually  hard,  the  tension 
increased,  and  the  vessel-wall,  as  a  rule,  thickened.  Hyper- 
trophy of  the  left  side  of  the  heart  occurs,  to  overcome  the 
resistance  offered  in  the  arteries  ;  and  in  many  cases  a  sys- 
tolic murmur  develops  at  the  apex,  probably  as  a  result  of 
relative  insufficiency.  Bronchitis  is  a  frequent  accompani- 
ment, especially  in  winter.  Sudden  attacks  of  oppressed 
breathing,  particularly  at  night,  are  not  infrequent.  Cheyne- 
Stokes  breathing  may  be  present,  most  commonly  toward 
the  close,  but  the  patient  may  be  walking  about  and  even 
attending  to  business.  Dyspepsia  and  loss  of  appetite  are 
common  ;  in  fact,  severe  vomiting  may  be  the  first  symptom. 
Severe  and  fatal  diarrhea  may  develop  ;  the  breath  is  often 
heavy  and  urinous.  Headache  is  frequently  an  early  and 
persistent  feature  of  chronic  interstitial  nephritis.  Hemor- 
rhages may  take  place  into  the  meninges  or  the  cerebrum  ; 
such  are  usually  associated  with  marked  changes  in  the 
walls  of  the  vessels.  Disorders  of  vision  may  be  one  of  the 
first  symptoms  of  the  disease,  and  the  oculist  may  be  the 
first  to  make  the  diagnosis  of  a  chronic  form  of  renal 
disease.  Ringing  in  the  ears,  with  dizziness,  is  not  un- 
common. 

Edema,  except  very  slight  swelling  of  the  ankles,  is  very 
uncommon  in  chronic  interstitial  nephritis  until  late  in  the 
disease,  when  it  is  probably  due  to  an  uncompensated 
heart.  The  skin  is  often  dry  and  pale.  Epistaxis  may 
occur  and  prove  serious.  Uremic  symptoms,  some  of 
which  have  been  mentioned,  are  common  in  the  advanced 
stage  of  the  disease.  Uremic  convulsions  may  be  frequent 
and  severe. 

Duration. — A  chronic  interstitial  nephritis  is  usually  in 
progress  for  many  years — from  ten  to  thirty,  or  a  longer 
time.  It  is  most  common  in  middle  life,  and  if  discovered 
early  and  the  source  determined,  by  good  care  the  patient 
may  have  fair  health  for  many  years. 


312      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

Prognosis. — The  prognosis  is  very  unfavorable,  although, 
as  has  been  stated,  if  the  disease  is  discovered  during  its 
early  stages,  the  patient  may  live  many  years.  Occasion- 
ally, the  patient  dies  of  some  intercurrent  disease  such  as 
pneumonia,  or,  perliaps  more  commonly,  cerebral  hemor- 
rhage because  of  the  diseased  arteries.  Frequently,  a  sud- 
den attack  of  uremia  results  fatally.  The  appearance  of 
waxy  casts  usually  indicates  that  the  fatal  termination  will 
occur  within  one  year,  and  often  within  six  months. 

Clinically,  an  uncomplicated  case  of  chronic  interstitial 
nephritis — that  is,  one  that  does  not  present  some  evidence 
of  a  slight  parenchymatous  change  (presence  of  fat) — is 
quite  uncommon,  it  being  the  rule  to  find  rarely  a  fat 
globule  adherent  to  an  occasional  cast. 

Differential  Diagnosis. — The  diagnosis  of  an  early  stage 
of  chronic  intei'stitial  nepJiritis  from  the  urine  alone  is  often 
difficult,  owing  to  the  fact  that  the  urine  is  so  slightly 
altered  from  the  normal.  It  is  at  this  time  that  a  very  care- 
ful consideration  of  the  clinical  history  and  the  physical 
examination  are  of  infinite  importance.  It  is  needless  to  say 
that  an  early  recognition  of  this  form  of  nephritis  is  very 
important,  for  if  it  is  the  result  of  some  chronic  irritation,  as 
by  lead  or  uric  acid,  the  same  should  be  recognized  and  the 
irritant  removed  as  early  as  possible. 

The  so-called  "cardiac  and  renal  "  cases  are  worthy  of 
consideration  here  because  of  the  differential  diagnosis 
between  a  chronic  interstitial  nepJiritis  and  passive  hyperemia. 
The  latter  condition  is  sometimes  superimposed  on  the 
former  because  of  an  uncompensated  heart.  From  the 
urine  alone  it  is  often  impossible  to  decide  which  con- 
dition is  the  more  prominent.  A  very  small  twenty-four- 
hour  quantity  of  urine,  a  comparatively  small  amount  of 
albumin  (trace),  and  the  presence  of  marked  edema  are  all 
against  a  chronic  nephritis.  On  the  other  hand,  if  the  sedi- 
ment contains  waxy  casts,  or  casts  from  extensively  denuded 
tubules,  very  granular  renal  cells,  and,  clinically,  a  high 
tension  pulse,  and  other  evidences  of  increased  blood  pres- 
sure, the  condition  may  be  a  chronic  interstitial  nephritis  in 
a  late  stage,  and  at  a  time  in  the  disease  when  the  edema  is 
the  direct  result  of  the  secondary  disease  of  the  heart.  It 
is  sometimes  necessary  to  watch  the  effect  of  treatment  by 
digitalis  or  other  drugs  that  act  chiefly  on  the  diseased 
heart  before  deciding  as  to  the  probability  of  an  underlying 


SENILE  INTERSTITIAL  NEPHRITIS.  313 

chronic  interstitial  nephritis.  If  the  original  abnormal 
features  of  the  urine  were  the  results  of  a  passive  congestion, 
such  abnormalities  will  usually  largely  disappear  as  the  con- 
dition of  the  heart  improv^es  by  treatment. 

It  is  often  difficult,  if  not  impossible,  to  distinguish  between 
an  active  hyperemia  attended  with  low  metabolism,  and  a  late 
stage  of  a  chronic  interstitial  nephritis  attended  witli  a  very 
slight  acute  process  and  without  the  presence  of  waxy  casts 
in  the  sediment.  About  five  years  ago  the  author  examined 
the  urine  of  a  man,  aged  seventy,  in  which  the  urinary  picture 
was  quite  typical  of  an  active  hyperemia.  Uremic  coma 
developed  two  da}"s  later  and  death  followed.  At  the 
autopsy  very  small,  red,  granular  kidneys  were  found, 
indicative  of  a  marked  chronic  interstitial  nephritis.  Of 
course,  in  such  cases,  a  knowledge  of  the  clinical  history 
and  the  physical  examination  are  of  the  greatest  importance. 

The  usual  prominent  signs  and  symptoms  of  a  chronic 
nephritis  will,  in  most  cases,  serve  to  establish  the  diag- 
nosis. 

SENILE  INTERSTITIAL  NEPHRITIS. 

Synonym. — Senile  atrophy  of  the  kidneys. 

This  form  of  disease  usually  occurs  in  persons  after  the 
age  of  from  fifty  to  sixty  ;  but  the  disease  is  not  necessarily 
present  in  every  elderly  person.  It  is  usually  a  part  of  the 
general  degeneration  of  the  blood-vessels  and  sometimes  a 
part  of  a  general  arteriosclerosis. 

In  the  senile  kidney  the  chief  lesions  are  those  due  to 
disease  of  the  vessels.  These  vascular  lesions  are  accom- 
panied by  impairment  in  the  power  of  regeneration.  Pre- 
vious lesions  of  the  kidney,  even  though  slight  in  character, 
may  gradually  make  their  influence  felt  in  impairing  the 
resistance  of  the  tissue.  The  epithelial  lesions  may  consist 
chiefly  in  atrophy.  Microscopically,  the  kidney  is  usually 
more  or  less  injected  and  atrophied.  On  microscopic  exam- 
ination the  epithelium  of  the  tubules  is  degenerated,  small, 
and  atrophic.  The  formation  of  yellow  pigment  in  the 
atrophic  epithelium  is  frequently  seen.  There  is  some  gen- 
eral increase  in  the  connective  tissue,  but  this  is  chiefly 
marked  close  beneath  the  capsules,  and  may  extend  from 
here  in  lines  into  the  cortex  (Councilman). 

Character  of  the  Urine. — The  urine  does  not  bear  the 
usual    characteristics     of    the    typical     chronic     interstitial 


314      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

nephritis,  but  has  more  the  appearance  of  a  passive 
hyperemia. 

The  quantity  is  generally  not  far  from  i  500  c.c.,  and  may 
even  be  considered  below  the  normal. 

The  albumin  is,  ordinarily,  from  the  slightest  possible  trace 
to  a  trace. 

The  normal  solids  are  absolutely  diminished,  but  no  more 
than  would  be  expected  in  a  person  of  advanced  years 
when  the  metabolism  is  decidedly  low.  Relatively,  they  are 
about  normal. 

The  sediment  has  practically  the  same  appearance  as  in 
the  early  form  of  chronic  interstitial  nephritis — an  occa- 
sional hyaline  and  granular  cast  and  granular  renal  cell. 

It  may  be  impossible  from  the  urine  alone  and  without  a 
knowledge  of  the  case  to  make  a  positive  diagnosis  of  a 
senile  interstitial  nephritis. 

CHRONIC   DIFFUSE   NEPHRITIS. 

Synonym. — Chronic  diffuse  nephritis  with  exudation. 

Chronic  diffuse  nephritis  is  undoubtedly  one  of  the  most 
common  of  the  chronic  diseases  of  the  kidney. 

From  a  clinical  point  of  view,  this  form  of  disease  par- 
takes essentially  of  two  pathologic  conditions  :  ( i)  An  inter- 
stitial element,  which  is  generally  very  prominent  and  shown 
by  the  increased  twenty-four-hour  quantity,  pale  color,  low 
specific  gravity,  increased  indoxyl,  and  relatively  and  abso- 
lutely diminished  normal  solids  ;  (2)  a  parenchymatous  ele- 
ment, shown  by  the  comparatively  high  percentage  of  albu- 
min and  the  presence  of  fatty  renal  elements  (fatty  casts, 
fatty  renal  cells,  etc.)  in  the  sediment.  Usually,  the  inter- 
stitial element  is  predominant,  hence  the  characteristic 
features  of  the  disease  in  a  general  way  resemble  those  of  a 
chronic  interstitial  nephritis. 

Pathologically,  the  morbid  processes  in  the  kidney  may 
consist  of  any  one,  or  a  combination  of  any,  of  the  following 
conditions  :  Chronic  glomerular  nephritis,  chronic  arterio- 
sclerotic nephritis,  chronic  degenerative  and  interstitial  neph- 
ritis. 

In  chronic  glomerular  nepliritis  the  essential  lesions  are 
in  the  glomeruli,  and  consist  of  extensive  hyaline  degenera- 
tion of  tufts  and  of  entire  glomeruli,  and  obliteration  of 
capillaries.      Every  transition  may  be  seen  between  these 


CHRONIC  DIFFUSE  NEPHRITIS.  315 

glomerular  lesions  and  those  in  the  subacute  form  of  neph- 
ritis. There  may  be  some  increase  in  the  capsular  epithe- 
lium and  connective-tissue  formation  within  the  capsule. 
The  tubular  epithelium  shows  extensive  degeneration  and 
destruction.  Entire  tubules  are  destroyed,  often  being  rep- 
resented by  the  thickened  irregular  membrana  propria. 
There  is  a  general  and  diffuse  increase  of  the  connective 
tissue  affecting  almost  equally  all  parts  of  the  kidney.  This 
condition  is  usually  found  as  an  independent  affection,  or  it 
may  be  combined  with  acute  infections  of  various  sorts, 
when  there  is  often  a  history  that  points  to  a  previous  acute 
or  subacute  affection.  The  kidney  may  be  slightly  larger 
than  normal,  of  normal  size,  or  considerably  smaller  than 
normal.  The  capsule  is  often  adherent,  the  surface  even,  not 
granular,  and  pale.  On  section,  the  cortex  varies  in  width  ; 
it  may  be  quite  small,  opaque,  whitish,  the  markings  obscure, 
the  glomeruli  not  visible  nor  pale,  and  the  consistence  of  the 
tissue  greatly  increased  (Councilman). 

(For  the  pathologic  description  of  chronic  arteriosclerotic 
nephritis  and  of  chronic  degenerative  and  interstitial  neph- 
ritis, see  pp.  305,  306.) 

Causes. — The  causes  of  a  chronic  diffuse  nephritis  are, 
in  some  instances,  probably  the  same  as  those  of  chronic 
interstitial  nephritis.  The  disease  sometimes  follows  an 
acute  nephritis  in  which  the  stage  of  convalescence  has  been 
prolonged  for  many  months  or  years.  The  author  has 
met  with  a  few  cases  in  which  a  chronic  diffuse  nephritis 
followed  an  acute  nephritis  of  pregnancy. 

Prominent  Symptoms. — In  the  majority  of  cases  of 
chronic  diffuse  nephritis  the  symptoms  are,  in  many  respects, 
the  same  as  in  chronic  interstitial  nephritis.  But  in  this  dis- 
ease there  is  constantly  more  or  less  edema,  which  is  usu- 
ally slight  during  the  early  stages,  becoming  more  marked 
as  the  disease  advances,  when  general  dropsy  may  be 
extreme.  There  is  usually  gastric  disturbance  and  fre- 
quency of  micturition,  accompanied  by  an  increase  in  the 
daily  quantity.  Circulatory  disturbances  are  more  or  less 
marked,  especially  when  the  disease  forms  a  part  of  a 
general  arteriosclerosis.  Anemia,  a  pasty  appearance  of 
the  skin,  emaciation,  and  visual  disorders  are  not  uncom- 
mon. Uremic  symptoms  are  frequently  met  with,  especial- 
ly in  advanced  cases,  or  as  the  result  of  acute  exacerba- 
tions. 


316      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

The  characteristics  of  the  urine  of  the  average  advanced 
case  of  chronic  diffuse  nephritis  are  as  follows  : 

Character  of  the  Urine. — Quantity. — The  average 
quantity  is  about  2000  c.c.  It  may  be  considerably 
higher — 3000  c.c. — or  lower, — 1500  c.c, — and  it  may  oc- 
casionally be  below  the  normal,  but  only  temporarily.  The 
quantity  of  urine  at  night  often  exceeds  that  of  the  day. 

Color. — Pale  and  sometimes  greenish. 

Specific  Gravity. — Average  loio  to  1015.  If  the 
twenty-four-hour  quantity  is  unusually  high,  the  specific 
gravity  may  be  from  1004  to  1008. 

Normal  Solids. — Absolutely,  diminished  and  sometimes 
to  a  marked  degree ;  relatively,  much  diminished.  The 
indoxyl  is  generally  normal  or  increased. 

Albumin. — This  varies  between  a  large  trace  and  3^  of  i 
per  cent.,  but  the  average  is  usually  between  y^  and  J^  of 
I  per  cent.  The  quantity  of  albumin  is  much  larger  than 
in  chronic  interstitial  nephritis  and  smaller  than  in  subacute 
glomerular  nephritis. 

Sediment. — This  is  generally  slight  in  quantity,  and  con- 
sists of  numerous  hyaline  and  granular  casts,  mostly  with 
fat  adherent  ;  an  occasional  (or  few)  fatty  cast ;  numerous 
renal  cells,  most  of  which  are  fatty,  and  a  few  compound 
granule  cells.  No  blood  is  seen  unless  complicated.  If  the 
disease  is  far  advanced,  a  few  waxy  casts  will  be  found  ; 
occasionally,  they  are  present  in  large  numbers.  When 
waxy  casts  appear  in  the  sediment,  the  twenty-four-hour 
quantity  of  urine  will  usually  be  less  than  normal. 

In  case  the  parenchymatous  element  predominates  the 
quantity  of  urine  will  be  not  far  from  the  normal  (1500 
c.c),  the  specific  gravity  and  quantity  of  albumin  will  be 
correspondingly  high,  and  the  amount  of  fat  in  the  sediment 
will  be  greater  than  indicated  above.  If,  on  the  other  hand, 
the  interstitial  element  predominates,  the  quantity  of  urine 
will  be  large  (2500  to  3000  c.z>^,  the  specific  gravity  and 
quantity  of  albumin  correspondingly  low,  and  the  amount 
of  fat  comparatively  small. 

Differential  Diagnosis. — In  the  diagnosis  of  chronic 
diffuse  nephritis  special  attention  should  be  paid  to  the 
twenty-four-hour  quantity  of  urine,  which,  if  permanently 
increased,  will  usually  serve  to  distinguish  it  from  a  subacute 
glomerular  nephritis.  In  some  instances  of  chronic  diffuse 
nephritis,  notably  following  an  acute  exacerbation  while  the 


AMYLOID  INFILTRATION.  317 

dropsy  is  still  marked,  the  total  quantity  of  urine  is  often 
less  than  normal,  the  quantity  of  albumin  is  very  large,  and 
the  amount  of  fat  is  excessive.  Under  these  circumstances 
it  is  usually  impossible  from  the  urine  alone  to  distinguish 
the  condition  from  a  subacute  glomerular  nephritis,  without 
watching  the  urine  for  a  considerable  period.  It  is  often 
impossible  to  differentiate  between  a  chronic  diffuse  nephritis 
near  death,  and  a  subacute  glomerular  nephritis  also  near 

death.  ,    •  ■    •      ,•    • 

An  nncomplicatcd  chronic  interstitial  nephritis  is  distin- 
guished from  a  chronic  diffuse  nephritis  by  the  presence  of 
fat  in  the  sediment,  the  comparatively  high  quantity  of 
albumin,  and,  upon  physical  examination,  the  presence  of 
edema  in  the  latter  disease. 

The  duration  of  chronic  diffuse  nephritis  will  depend 
largely  on  whether  the  interstitial  or  the  parenchymatous 
element  predominates.  If  the  former,  the  patient  may  live 
from  ten  to  fifteen  years,  providing  he  has  the  best  of  care  ; 
on  the  other  hand,  if  the  parenchymatous  element  is  pre- 
dominant, the  duration  of  life  is  usually  between  five  and 
ten  years.  As  in  subacute  glomerular  nephritis,  acute  ex- 
acerbations are  very  likely  to  occur,  and  if  they  are  very 
numerous,  the  duration  of  life  may  not  exceed  from  five  to 
eight  years,  and  often  death  occurs  within  a  much  shorter 

period. 

The  prognosis  is,  in  most  cases,  grave.  The  appearance 
of  waxy  casts  in  the  sediment  is  an  unfavorable  sign  ;  death 
will  probably  occur  within  one  year. 

AMYLOID  INHLTRATION. 

Synonyms.— Lardaceous  kidney  ;  waxy  degeneration  ; 
chronic  depurative  disease  of  the  kidneys. 

Amyloid  infiltration  is  a  disease  that  is  not  confined  alone 
to  the  kidneys.  The  lesions  are  usually  prominent  in  other 
organs  of  the  body  as  well— notably  the  liver  and  spleen. 

In  amyloid  infiltration,  as  the  name  implies,  the  character- 
istic lesion  is  the  amyloid  infiltration  about  the  blood-vessels  ; 
consequently,  the  portion  of  the  kidney  that  is  most  seriously 
affected  is  the  glomerulus.  There  may  be  small  masses  of 
amyloid  along  the  vascular  loops,  or  the  entire  glomerulus 
may  be  converted  into  a  glassy,  homogeneous  mass,  the 
result  of  the   deposit  of  the  amyloid  material.     Usually, 


318      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

some  of  the  glomeruli  are  only  moderately  affected,  hence 
the  functions  of  the  kidneys  are  maintained  for  some 
period. 

The  amyloid  material  is  stained  a  mahogany-brown  color 
by  iodine,  whereas  the  unaffected  tissue  takes  a  dehcate 
yellow  stain  ;  and  a  rose-red  color  by  methyl-violet,  the 
undiseased  tissue  being  stained  blue. 

Causes. — Amyloid  infiltration  is  often  an  accompaniment 
of  syphilis,  phthisis,  tubercular  disease  of  the  joints,  chronic 
suppuration  of  the  bones,  and  chronic  wasting  diseases.  The 
exact  reason  for  amyloid  infiltration  in  these  conditions  is 
not  known. 

Prominent  Symptoms. — The  features  of  the  urine  alone 
may  not  definitely  indicate  the  presence  of  this  disease. 
Usually,  the  associated  conditions  (syphilis,  tuberculosis, 
etc.)  give  hints  as  to  the  nature  of  the  process.  The  liver 
and  spleen  are  usually  enlarged.  Diarrhea  is  a  common 
symptom.  Increased  arterial  tension  and  cardiac  hyper- 
trophy are  not  usually  present,  except  in  those  cases  in 
which  amyloid  infiltration  occurs  in  the  secondary  con- 
tracted kidney.  Under  these  circumstances  there  may  be 
uremia  and  retinal  changes,  which,  as  a  rule,  are  not  met 
with  in  uncomplicated  amyloid  infiltration.  Frequency  of 
micturition  and  the  elimination  of  a  large  quantity  of  urine 
in  twenty-four  hours  are  often  important  and  early  signs. 
It  is  essential  that  the  clinical  history,  the  physical  examin- 
ation, and  the  urine  should  receive  equal  weight  in  the  diag- 
nosis of  amyloid  infiltration  ;  it  rarely  happens  that  the  urine 
alone  affords  sufficient  data  for  an  accurate  diagnosis. 

Character  of  the  Urine. — The  urine  of  a  well-advanced 
case  of  amyloid  infiltration  is  as  follows  : 

Quantity. — Usually,  above  1 500  c.c.  ;  generally,  between 
2000  and  4000  c.c.  The  quantity  of  the  day  urine  usually 
exceeds  that  of  the  night.  Like  the  other  chronic  affec- 
tions of  the  kidneys,  the  quantity  generally  falls  to  normal 
or  below  the  normal  a  short  time  before  death. 

Color. — Generally,  very  pale  ;  the  urine  often  has  a 
greenish  tint. 

Specific  Gravity. — This  is  below  the  normal  ;  it  is  usu- 
ally found  to  vary  between  10 12  and  1018. 

Normal  Solids. — Absolutely,  normal  or  slightly  dimin- 
ished, but  dependent  upon  the  metabolism.  Relatively, 
much  diminished,  especially  if  the  Quantity  of  urine  be  very 


AMYLOID  INFILTRATION.  319 

large.  The  probable  explanation  of  the  normal  quantity  of 
solids  in  the  urine  is  the  fact  that  the  parenchyma  or  secret- 
ing structure  of  the  kidney  does  not  become  involved  until 
late  in  the  disease,  the  principal  pathologic  changes  being 
about  the  blood-vessels.  Absolutely,  the  indoxyl  may  be 
increased,  but  it  is  usually  diminished. 

Albumin. — In  an  uncomplicated  case  the  quantity   of 
albumin  varies  between  a  trace  and  yi  of  i  per  cent.  ;  only 
rarely  does  it  exceed  yi  of  i  per  cent.      On  the  other  hand 
it  may  be  less  than  a  trace,  particularly  if  the  quantit}^  of 
urine  is  in  the  neighborhood  of  4000  c.c. 

Sediment. — This  is  generally  very  slight  in  amount,  and 
consists  of  a  few  hyaline,  granular,  and  occasional  (or  few) 
waxy  casts  ;  rarely,  a  renal  cell.  No  fat  nor  blood,  unless 
complicated. 

The  waxy  casts  appear  rather  early  in  this  disease,  much 
sooner  than  in  the  other  chronic  diseases  of  the  kidney. 
The  question  has  often  arisen  as  to  whether  the  waxy  casts 
found  in  amyloid  disease  were  cylinders  of  amyloid  material 
or  of  the  same  composition  as  those  found  near  the  end  of 
other  chronic  affections  of  the  kidney  ?  The  quer>'  still 
remains  unsettled,  for  the  reason  that  it  is  very  difficult  to 
satisfactorily  stain  the  waxy  casts  by  the  stains  ordinarily 
used  for  the  detection  of  amyloid  material.  If  the  suspected 
sediment  is  first  washed  several  times  by  decantation  with  a 
dilute  solution  of  glycerine,  and  methyl-violet  added,  some 
of  the  casts  (both  waxy  and  hyaline)  will  be  found  to  have 
a  slight  reddish  tint.  Further  experiments  are,  however, 
necessary  before  any  definite  conclusions  can  be  drawn  from 
the  use  of  stains. 

Amyloid  disease  of  the  kidney  is  Axry  apt  to  be  compli- 
cated by  parenchymatous  degeneration  ;  such  changes  are 
probably  secondary  to  the  extensive  deposit  of  amyloid 
material  in  the  glomeruli  and  the  resulting  interference  with 
the  nutrition  of  the  renal  epithelium.  Sometimes  this 
parenchymatous  change  is  very  marked,  so  that  the  urine 
will  have  the  characteristics  of  chronic  diffuse  nephritis  ;  or 
it  may  predominate  to  such  an  extent  that  the  urine  will 
resemble  one  of  subacute  glomerular  nephritis,  the  evi- 
dences of  amyloid  being  thereby  obscured. 

Differential  Diagnosis. — In  the  diagnosis  between  an 
U7icoinplicated  amyloid  infiltration  and  a  chronic  interstitial 
nephritis  \.\\Q  enlarged  liver  and  spleen,  an  absence  of  increased 


320      DISTURBANCES  AND  DISEASES  OF  THE  KIDNEYS. 

arterial  tension  and  cardiac  hypertrophy,  and  the  history 
of  syphiHs,  tuberculosis,  etc.,  will  usually  indicate  amyloid 
disease.  From  the  urine  alone  it  is  impossible  to  distin- 
guish with  certainty  between  these  two  conditions.  It 
should  be  said,  however,  that  in  amyloid  infiltration  the 
total  solids  and  the  total  quantity  of  urea  are  usually 
higher  than  in  chronic  interstitial  nephritis,  but  such  a  rule 
is  by  no  means  invariable,  since  amyloid  disease  is  often  ac- 
companied by  a  chronic  disease  that  very  much  diminishes 
the  metabolism. 

As  previously  stated,  in  considering  the  diagnosis  of  this 
disease  the  physical  examination  and  clinical  history  should 
always  be  carefully  weighed  along  with  the  characteristics 
of  the  urine. 

The  duration  of  this  disease  is  largely  dependent  on  the 
cause.  As  a  rule,  it  extends  over  a  period  of  several  years 
— from  ten  to  fifteen  ;  sometimes  a  longer,  and  occasionally 
a  much  shorter,  time. 

The  prognosis  depends  rather  on  the  condition  with 
which  this  renal  affection  is  associated.  As  a  rule,  it  is 
erave. 


CHAPTER  IX. 


DISEASES  OF  THE  KIDNEYS  (CONTINUED), 

TUBERCULOSIS  OF  THE  KIDNEYS. 

Primary  tuberculosis  of  the  kidneys  is  not  very  rare.  It 
occurs  in  two  distinct  forms — viz.,  local  caseating  tuberculo- 
sis and  acute  miliary  tuberculosis.  The  latter  form  is  always 
associated  with  tuberculosis  in  other  parts  of  the  body,  such 
as  phthisis  pulmonalis  and  tubercular  meningitis.  This 
form  rarely  gives  rise  to  distinct  urinary  symptoms.  Local 
caseating  tuberculosis,  on  the  other  hand,  usually  results  in 
urinary  symptoms  to  a  marked  degree,  and  it  is  this  form 
that  deserves  special  consideration  in  this  connection. 

The  substance  of  the  kidney  may  contain  only  a  few,  or 
there  may  be  a  large  number  of,  tubercular  nodules.  The 
process  very  soon  involves  the  pelvis  of  the  kidney,  and  in  a 
majority  of  the  cases  not  only  the  pelvis  but  the  ureter  as 
well,  and  sometimes  the  bladder  and  prostate.  It  may  be 
difficult  to  say  in  advanced  cases  whether  the  disease  has 
started  in  the  bladder,  prostate,  or  seminal  vesicles,  and  crept 
up  the  ureters,  or  whether  it  started  in  the  kidneys  and  pro- 
ceeded downward.  Osier  believes  that  in  the  majority  of  cases 
the  latter  is  true,  and  the  infection  is  through  the  blood.  One 
kidney  alone  may  be  involved,  and  the  disease  creeps  down 
the  ureter  and  may  involve  the  mucous  membrane  of  the 
bladder  to  a  greater  or  less  extent.  The  process  is  com- 
mon in  the  middle  period  of  life,  but  it  may  occur  in  the 
extremes  of  age.  It  is  more  frequent  in  males  than  in 
females. 

Prominent  Symptoms. — The  symptoms  are  usually 
those  of  chronic  pyelitis.  The  urine  may  be  purulent  for 
years,  and  there  may  be  little  or  no  distress.  Even  before 
the  bladder  becomes  involved  micturition  is  often  frequent, 
and  many  instances  are  mistaken  for  cystitis.  The  condJ- 
21  321 


322  DISEASES  OF  THE  KIDNEYS. 

tion  may  be  in  progress  for  many  years  without  marked 
impairment  of  health.  In  cases  in  which  the  disease  be- 
comes advanced  and  both  organs  are  affected,  constitutional 
symptoms  are  more  marked.  General  tuberculosis  is  com- 
mon. Intermittent  hematuria  is  of  frequent  occurrence, 
denoting  ulcerative  changes  in  the  mucous  membrane  of  the 
tubules  of  the  kidney. 

Physical  examination  may  detect  special  tenderness  on 
one  side,  or  the  kidney  may  be  palpable  in  front  on  deep 
pressure  ;  but  a  tuberculous  kidney  seldom  causes  a  large 
tumor.  Occasionally,  the  ureter  becomes  occluded  and 
pyonephrosis  results  ;  but  this  is  rare  in  comparison  with  its 
frequency  in  calculous  pyelitis. 

Character  of  the  Urine. — Early  in  tuberculosis  of  the 
kidney  the  urine  is  only  slightly  altered  from  the  normal. 
There  may  be  the  slightest  trace  of  albumin,  and  the  sedi- 
ment may  contain  only  a  very  few  leucocytes  and  an  occa- 
sional blood  globule.  When,  however,  the  disease  becomes 
more  advanced  and  ulcerative  changes  have  begun,  the 
urine  will  usually  have  the  following  characteristics  : 

Quantity. — The  total  quantity  of  urine  for  twenty-four 
hours  is  generally  increased,  although  it  may  be  normal  or 
diminished. 

Color. — Pale.  The  urine  is  usually  more  or  less  turbid, 
due  to  the  pus,  blood,  etc.,  in  suspension. 

Reaction. — Generally  acid,  except  when  the  urine  con- 
tains an  abundance  of  blood,  when  it  may  be  faintly  acid  or 
alkaline. 

Specific  Gravity. — Usually  below  the  normal — loio  to 
loi  5,  or  thereabouts. 

Normal  Solids. — Both  relatively  and  absolutely,  dimin- 
ished. If  there  is  general  advanced  tuberculosis,  the  solids 
will  be  absolutely  very  low. 

Albumin. — The  quantity  of  albumin  is  dependent,  in  the 
first  place,  on  the  amount  of  destruction  of  the  kidney,  and, 
secondly,  on  the  amount  of  pus  and  blood  present.  If  the 
disintegration  of  the  renal  tissue  is  marked,  the  albumin  is 
usually  high,  approximating  from  ^  to  ^  of  i  per  cent. 
If,  on  the  other  hand,  the  tubercular  process  is  localized  and 
not  extensive,  the  amount  of  albumin  may  not  exceed  a 
slight  ti'ace,  or  trace. 

Sediment. — Abundant.  Chiefly  pus,  which  is  usually 
free,  but  may  be  more  or  less  clumped  ;  the  pus  may  be 


TUBERCULOSIS  OF  THE  KIDNEYS.  323 

markedly  degenerated.  Many  small  round  cells,  some  of 
which  are  usually  fatty.  Hyaline  and  granular  casts,  some 
of  larger  diameter,  are  usually  present,  but  they  may  be  so 
obscured  by  the  pus  as  to  escape  detection.  Blood  is  gen- 
erally present,  but  sometimes  in  small  amount  ;  it  may, 
however,  be  very  abundant,  intermittent  hematuria  being  a 
common  symptom  of  this  disease.  The  sediment  also  con- 
tains tubercle  bacilli. 

To  distinguish  the  condition  from  a  calculous  p)'elitis  is 
often  difficult.  Hemorrhage  may  be  present  in  both  condi- 
tions, though  not  nearly  so  frequently  in  the  tuberculous 
disease.  The  diagnosis  rests  on  three  points  :  ( i )  The 
detection  of  some  focus  of  tuberculosis,  as  in  the  testes  ;  (2) 
the  presence  of  tubercle  bacilli  in  the  sediment ;  and  (3)  the 
use  of  tuberculin.  In  women  the  kidney  involved  is  now 
easily  determined  by  catheterizing  the  ureters  after  the  plan 
introduced  by  Kelly,  of  Baltimore.  Dr.  Edw.  Reynolds, 
has  recently  reported  a  case  of  early  tuberculosis  of  the 
kidney,^  in  which  the  author  had  the  opportunity  of 
making  a  careful  study  of  the  urine,  and  in  which  cathet- 
erization of  the  ureters  led  to  the  location  of  the  disease. 

Detection  of  Tubercle  Bacilli  in  the  Urinary  Sediment. 

Either  centrifugalize  the  urine  or  allow  the  sediment  to 
settle  by  gravity  ;  decant  the  supernatant  urine,  and  wash 
twice  by  decantation  with  distilled  water.  After  the  second 
washing,  centrifugalize.  The  sediment  is  then  taken  up  by 
means  of  a  pipette  and  placed  on  from  four  to  eight  cover- 
glasses,  which  have  been  carefully  cleansed  in  nitric  acid 
and  then  in  alcohol.  Care  should  be  exercised  not  to  get 
too  much  sediment  on  the  cover-glasses,  for  the  layer  may, 
after  drying,  be  too  thick,  especially  if  there  is  much  pus  in 
the  sediment.  These  cover-glass  preparations  are  then 
dried  by  placing  them  on  an  iron  or  copper  plate,  under 
which  is  placed  a  very  small  flame  (about  y^  of  an  inch 
in  height  will  suffice),  the  main  object  being  to  get  very 
gentle  heat  so  that  the  specimens  will  be  dried  slowly 
and  without  being  charred.  Stain  the  dried  preparations 
with  either  carbol-fuchsin  (Ziehl-Neelson)  or  aniline  water 
and  fuchsin  (Koch-Ehrlich)  in  the  usual  manner.  Decolor- 
ize in  20  per  cent,  nitric  acid,  wash  in  water,  and,  finally,  still 

1"  Johns  Hopkins  Bulletin,"  Nov.,  1898,  p.  253. 


324  DISEASES  OF  THE  KIDNEYS. 

further  decolorize  in  jo  per  cent,  alcohol  for  at  least  ten 
minutes.  Then  stain  with  an  aqueous  solution  of  methylene- 
blue,  mount,  and  examine. 

It  is  very  important  that  the  preparations  should  be 
thoroughly  decolorized  in  alcohol  in  order  to  be  able  to 
distinguish  between  tubercle  bacilli  and  smegma  bacilli ; 
the  latter  being  quite  readily  decolorized  by  this  means, 
while  the  former  are  not  affected.  A  very  close  resem- 
blance exists  between  these  two  organisms.  At  times  the 
smegma  bacillus  appears  thicker  than  the  tubercle  bacillus, 
and  sometimes  the  ends  have  a  clubbed  appearance,  but 
this  is  not  true  in  all  instances  ;  consequently,  the  data  thus 
far  at  hand  are  of  no  differential  importance.  Smegma 
bacilli  are  not  uncommon  in  the  urine  of  both  male  and 
female,  particularly  in  the  urine  of  those  who  are  not 
cleanly.  It  is  obvious  that  special  care  should  be  taken  in 
procuring  a  specimen  that  is  to  be  examined  for  tubercle 
bacilli.  Since  in  those  individuals  who  are  not  cleanly  the 
smegma  collect  about  the  genitalia,  it  is  essential  that  these 
parts  be  thoroughly  cleansed  before  the  urine  is  voided.  A 
still  better  procedure  is  to  procure  a  catheter  specimen,  if 
possible.  Attention  to  these  details  contributes  materially 
to  a  satisfactory  result  of  the  examination. 

Tubercle  bacilli  in  the  urine  are  usually  arranged  in 
groups  (Plate  9),  although  they  may  occur  singly.  They 
may  be  present  in  large  numbers  and  easily  found  ;  on  the 
other  hand,  they  may  be  rare  and  escape  detection  even  after 
prolonged  examination.  The  fact  that  tubercle  bacilli  can  not 
be  found  in  a  urinary  sediment  does  not,  then,  prove  their 
absence.  In  all  suspicious  cases  a  portion  of  the  sediment 
(^  to  I  c.c.)  should  be  injected  into  the  peritoneal  cavity 
of  a  guinea-pig.  If  the  bacilli  are  present,  the  animal  will 
develop  tuberculosis  in  from  six  to  eight  weeks  ;  if  not 
present,  the  animal  will  not  be  affected  by  the  inoculation. 
This  constitutes  the  safest  method  for  the  detection  of 
tubercle  bacilli  in  urine. 


RENAL  CALCULUS. 

Calculi  may  originate  in  the  secreting  structure  of  the 
kidney, — usually  in  the  tubules, — forming  cavities  for  their 
location  in  the  parenchyma  of  the  organ. 

Renal   calculus    is  usually  unilateral,   though   there  are 


Plate 


Tubp:rci.e  Bacilli  in  Urinary  Sediment 
Observation.) 


X  ^oo.     (Personal 


RENAL  CALCULUS.  325 

many  exceptions  to  this  rule.  The  calculus,  when  large,  is 
usually  single,  the  smaller  ones  being  more  apt  to  be 
multiple. 

Renal  calculus  occurs  at  all  ages,  including  intra-uterine 
life.  It  is,  however,  most  common  before  fifteen,  and  after 
fifty,  years  of  age.  In  young  people  and  children  calculi 
are  most  frequent  among  the  poor,  while  the  condition  in 
advancing  life  is  most  common  in  people  in  comfortable  cir- 
cumstances and  of  luxurious  habits.  As  a  rule,  the  calculi 
in  infency  are  composed  of  ammonium  urate ;  those  in 
young  adults,  uric  acid  ;  those  after  fifty  years  of  age  are 
made  up  of  either  uric  acid  or  calcium  oxalate. 

Prominent  Symptoms. — These  consist  of  dull  aching 
pain  situated  deeply  in  the  loin,  usually  unilateral,  and 
often  radiating  along  the  ureter  toward  the  testicle  or  labia, 
down  the  thigh,  and  sometimes  extending  as  far  as  the 
foot.  The  pain  may  be  sharp  and  lancinating  at  times. 
When  a  stone  enters  the  ureter,  intensely  severe  paroxysms 
of  pain  (renal  colic)  are  usually  experienced,  lasting  a  few 
hours  and  then  suddenly  subsiding.  The  ordinary  pain  of 
renal  calculus  is  nearly  always  increased  by  exercise — walk- 
ing or  riding.  There  is  often  tenderness  upon  deep  pressure 
anteriorly,  especially  if  the  calculus  has  excited  much  in- 
flammation. Gastric  disturbances  are  common,  includincr 
nausea,  vomiting,  and  periods  of  more  or  less  disordered 
digestion,  hyperacidity,  flatulence,  etc. 

Character  of  the  Urine. — The  urine  is  usually  highly 
concentrated,  of  high  color,  high  specific  gravity,  and  sharply 
acid  reaction.  Sometimes  it  has  a  decided  smoky  color, 
because  of  the  presence  of  altered  blood  pigment.  Rela- 
tively, the  solids  are  generally  increased  ;  absobitely,  about 
normal,  providing  the  patient  is  in  good  general  condition  ; 
as  a  rule,  the  normal  solids  will  depend  upon  the  meta- 
bolism. 

The  amount  of  albumin  depends  on  the  extent  of  the 
irritation  and  the  quantity  of  blood. 

The  sediment  is  usually  that  of  an  active  hyperemia  or 
irritation  of  the  kidneys.  It  is  not  uncommon  to  find  crys- 
tals or  microscopic  concretions  of  the  same  substance  as  the 
calculus  that  is  being  formed  in  the  kidney.  There  may  be 
a  considerable  quantity  of  blood,  which  is  usually  abnormal 
in  character,  providing  the  hemorrhage  is  not  abundant ;  if 
profuse,  there  is  generally  more  or  less  normal  blood.     The 


326  DISEASES  OF  THE  KIDNEYS. 

sediment  may  or  may  not  contain  pus.  It  is  more  common 
perhaps  to  find  only  a  few  leucocytes  rather  than  an  abun- 
dance of  pus.  If  much  pus  is  present,  it  is  probable  that 
either  an  abscess  of  the  kidney  or  a  chronic  pyelitis  has  been 
produced  by  the  stone. 

Renal  calculi  usually  consist  of  either  uric  acid  or  urates, 
calcium  oxalate,  or  cystin.  Occasionally,  the  calculus  is 
the  result  of  a  deposit  of  phosphates  in  the  kidney.  Such 
a  deposition  is  always  secondary  to  an  extension  upward 
from  the  bladder  or  pelvis  of  the  kidney.  In  case  of  a 
phosphatic  calculus  in  the  kidney  the  urine  is  usually  pale 
in  color,  with  an  alkaline  reaction,  and  an  abundant  deposit 
of  phosphates  in  the  urinary  sediment. 


ABSCESS  OF  THE  KIDNEY. 

Abscess  of  the  kidney  is  usually  due  either  to  injury  of 
the  organ,  to  an  encysted  concretion  that  sets  up  a  marked 
irritation  in  some  portion  of  the  kidney,  or  to  tubercular 
disease  of  the  organ. 

The  condition  is  accompanied  by  the  usual  symptoms  of 
an  abscess  in  any  part  of  the  body — viz.,  fever,  localized 
pain,  cachexia,  marked  languor,  nausea  and  vomiting,  etc. 
On  the  affected  side  there  may  be  a  distinct  tumor,  which, 
on  manipulation,  is  found  to  be  extremely  tender  ;  again,  the 
condition  may  exist  without  tumor. 

The  abscess  usually  ruptures  into  the  pelvis  of  the  kidney 
or  into  the  renal  tubules,  and  the  urine  that  was  free  from 
pus  will  suddenly  contain  a  large  amount  of  it. 

Character  of  the  Urine. — The  urine  generally  has  the 
characteristics  of  a  fever  urine — high  color,  high  specific 
gravity,  strongly  acid  reaction,  and  containing  a  very  slight 
trace  or  a  trace  of  albumin.  The  sediment  usually  has  the 
appearance  of  one  of  active  hyperemia,  which  may  be  mild 
or  severe,  according  to  the  extent  of  the  inflammatoiy 
process  (circumscribed  acute  nephritis)  about  the  abscess, 
and  the  degree  of  disturbance  that  is  invariably  set  up  as  a 
result  of  the  elimination  of  toxines  by  the  healthy  kidney. 
As  soon  as  the  abscess  evacuates  into  the  urinary  tract, 
the  sediment,  which  is  abundant  and  usually  of  a  greenish 
color,  contains  an  abundance  of  degenerated  pus,  many 
small  round  cells,  usually  a  few  compound  granule  cells, 
and  more  or  less  blood.     There  is  frequently  hematuria  fol- 


RENAL  EMBOLISM.  327 

lowing  the  evacuation  of  the  abscess,  especially  if  any  of 
the  renal  blood-vessels  have  been  ruptured.  This  hem- 
orrhage may  be  slight  and  of  short  duration  if  due  to 
injury  of  the  capillaries,  and  may  be  extensive  and  per- 
sistent if  one  or  more  of  the  larger  vessels  have  been 
ruptured. 

The  sudden  appearance  of  a  large  amount  of  blood  and 
pus  in  a  urine  that  has  previously  been  clear  and  free  from 
these  elements  is  strongly  suggestive  of  abscess  of  the 
kidney,  especially  when  taken  in  conjunction  with  the 
clinical  history  and  symptoms.  A  diagnosis  of  this  con- 
dition can  not  be  made  from  the  urine  alone  previous  to  the 
rupture  of  the  abscess  and  without  a  clinical  knowledge  of 
the  case. 

The  prognosis  is  usually  grave  when  the  disease  is  of 
tubercular  origin.  When  it  is  due  to  trauma  or  to  an 
encysted  concretion,  the  prognosis  is  often  good  if  an  early 
diagnosis  is  made.  Occasionally,  recovery  follows  drainage 
of  the  pus-sac,  and  in  rare  instances  spontaneous  recovery 
takes  place,  particularly  when  the  destructive  changes  are 
only  slight.  In  most  cases  of  abscess  of  the  kidney  sur- 
gical interference  is  necessary. 

RENAL  EMBOLISM. 

Renal  embolism  consists  of  an  impacted  thrombus  that 
has  formed  in  some  part  of  the  circulatory  system, — usually 
on  the  valves  of  the  heart, — and  is  carried  by  the  blood 
current  to  the  kidney,  where  it  occludes  one  of  the  renal 
■vessels.  The  anatomic  changes  resulting  from  renal  em- 
bolism are  very  constant  and  striking,  and  the  condition  is 
quite  commonly  found  at  the  autopsy,  although  only  rarely 
recognized  during  life. 

Prominent  Symptoms. — -A  previous  history  of  endo- 
carditis is  generally  found.  The  sudden  pain  that  usually 
accompanies  the  occlusion  of  the  renal  vessel  may  be 
severe,  often  followed  by  nausea  and  vomiting,  and  some- 
times by  a  state  of  collapse.  On  the  other  hand,  the  pain 
may  be  comparatively  slight,  although  usually  persistent 
for  some  time.  Chills  and  a  more  or  less  irregular  tem- 
perature are  frequent  accompaniments  of  this  condition. 

Character  of  the  Urine. — From  the  urine  alone  the 
diagnosis   of  a    renal   embolism    is   practically  impossible. 


328  DISEASES  OF  THE  KIDNEYS. 

The  urinary  changes  usually  begin  abruptly,  and  the  urine 
suddenly  has  the  characteristics  of  one  accompanying  fever. 
The  urine  is  usually  much  diminished  in  quantity,  of  high 
color,  and  high  specific  gravity — 1025  to  1035.  Rela- 
tively, the  normal  solids  are  increased  ;  absolutely,  normal  or 
slightly  diminished.  The  quantity  of  albumin  depends  upon 
the  extent  of  the  disturbance  in  the  neighborhood  of  the  area 
affected  by  the  embolus.  The  sediment  usually  has  the 
characteristics  of  a  more  or  less  severe  active  hyperemia 
or  a  circumscribed  acute  nephritis,  which  is  in  progress 
around  the  diseased  area. 


TUMORS   OF  THE  KIDNEY. 

These  are  benign  or  malignant.  Of  the  benign  tumors, 
the  most  common  are  the  fibromata ;  lipoinata,  lyjuph- 
adcnoniata,  and  angioniata  are  constantly  met  with.  Adeno- 
mata may  be  congenital.  Malignant  growths — sarco7)ia  or 
carcinoma — may  be  either  primary  or  secondary.  Sarcomata 
are  the  more  common. 

Tumors  of  the  kidney  grow  rapidly  and  may  attain  a 
very  large  size — 12  to  30  pounds.  They  are  often  soft, 
and  hemorrhages  frequently  occur  in  them.  In  sarcomata 
invasion  of  the  pelvis  or  of  the  renal  vein  is  common.  In 
almost  all  instances  tumor  is  present.  An  increasing  tumor 
in  the  anterior  lumbar  region,  between  the  costal  arch  and 
the  crest  of  the  ilium,  is  always  suggestive  of  renal  tumor. 
The  tumors  are  usually  fixed,  although  they  may  be  mov- 
able ;  they  are  frequently  lobulated. 

Prominent  Symptoms. — Hematuria. — This  may  be  the 
first  indication.  The  blood  is  fluid  or  clotted  ;  sometimes 
a  blood-clot  is  passed  having  the  appearance  of  a  cast  of 
the  ureter. 

Progressive  Emaciation. — Loss  of  flesh  is  usually  marked 
and  advances  rapidly. 

Pain. — This  is  generally  present,  and  of  a  dull  aching 
character,  situated  in  the  flank  and  radiating  down  the  thigh. 
The  pressure  of  the  tumor  often  causes  severe  and  alarming 
symptoms,  such  as  edema  of  the  feet  and  legs,  ascites,  dis- 
turbances of  the  stomach,  various  neuroses, — the  result  of 
pressure  on  the  large  nerve-trunks, — and  anemia.  There  is 
often  frequent  micturition,  which  may  be  so  marked  as  to  indi- 
cate a  disease  of  the  bladder  when  only  the  kidney  is  involved. 


CYSTIC  DISEASE  OF  THE  KIDNEYS.  329 

Character  of  the  Urine. — Perhaps  the  most  prominent 
feature  of  the  urine  is  the  presence  of  more  or  less  blood — 
hematuria ;  occasionally,  the  amount  of  fresh  blood  is 
very  large,  but  this  is  not  true  in  every  case.  The  urine 
usually  shows  evidence  of  a  circumscribed  inflammation  or 
congestion  of  the  kidney  in  the  neighborhood  of  the  new 
growth  :  in  other  words,  the  urine  presents  the  picture  of  a 
more  or  less  severe  active  hyperemia  of  the  kidney.  Pus  is 
generally  absent  in  the  sediment,  save  in  advanced  cases 
attended  with  decided  destructive  changes  in  the  kidney  or 
changes  in  the  new  growth  itself  Under  such  circum- 
stances the  quantity  of  pus  is  comparatively  small,  consider- 
ing the  extent  of  the  necrotic  changes.  Rarely,  cancer 
elements  can  be  recognized  in  the  urinary  sediment.  Occa- 
sionally, the  presence  of  a  large  number  of  epithelial  cells 
with  large  and  prominent  nuclei  and  of  various  shapes  is 
strongly  suggestive  of  new  growth,  especially  if  the  mucous 
membrane  of  the  pelvis  is  involved  or  has  become  ulcerated. 
The  presence  in  the  sediment  of  organized  elements,  such  as 
renal  casts,  renal  cells,  etc.,  is  of  little  or  no  diagnostic 
value  in  renal  cancer. 

A  diagnosis  of  renal  cancer  from  the  urine  alone  is  only 
of  the  rarest  occurrence,  and  then  only  in  case  particles  of 
the  morbid  growth  with  a  distinct  alveolar  structure  are 
discovered  in  the  sediment  ;  but  in  malignant  disease 
limited  to  the  parenchyma  of  the  kidney  the  appearance 
of  portions  of  the  growth  in  the  sediment  is  practically  un- 
known. 

CYSTIC  DISEASE  OF  THE  KIDNEYS. 

Cystic  disease  of  the  kidneys  is  probably  the  result,  in 
most  cases,  of  some  obstruction  to  the  outflow  of  urine 
through  one  or  more  renal  tubules.  Three  varieties  of 
cysts  are  met  with  : 

1.  Small  cysts,  seen  especially  in  chronic  interstitial  neph- 
ritis, resulting  from  dilatation  of  obstructed  tubules  or  Bow- 
man's capsule. 

2.  Solitary  cysts,  ranging  in  size  from  a  marble  to  an 
orange,  or  even  larger,  without  evidences  of  other  changes 
in  the  kidney. 

J.  Congenital  cystic  kidneys.  In  this  condition  the  kid- 
neys are  represented  by  a  conglomeration  of  cysts  varying 
in  size  from  a  pea  to  a  marble.    The  organs  are  greatly  en- 


330  DISEASES  OF  THE  KIDNEYS. 

larged,  and  together  may  weigh  from  seven  to  ten  pounds. 
In  the  fetus  they  may  attain  a  size  sufficient  to  impede 
labor.  Little  or  no  renal  tissue  may  be  noticeable,  although 
on  microscopic  examination  it  is  seen  that  a  considerable 
amount  remains  in  the  interspaces. 

The  cystic  fluid  is  usually  clear,  but  it  may  be  turbid,  and 
sometimes  reddish-brown  or  even  black  in  color ;  occasion- 
ally, it  is  viscid.  Specific  gravity  is  usually  low.  Albumin, 
blood-corpuscles,  and  sometimes  hematoidin  crystals,  leuco- 
cytes, cholesterin,  triple  phosphates,  and  fat  globules  are 
found  in  the  contents.  Urea  and  uric  acid  are  present 
only  in  traces.  The  contents  of  one  cyst  may  have  an 
entirely  different  character  from  those  of  an  adjacent  cyst. 

Character  of  the  Urine. — In  general  the  character  of 
the  urine  is  that  of  a  chronic  interstitial  nephritis.  In  some 
instances  the  urine  is  not  abnormal,  especially  in  those  cases 
in  which  there  are  no  other  changes  in  the  kidney. 

The  diagnosis  of  cystic  disease  of  the  kidney  can  not 
be  made  with  certainty  from  the  urine  alone.  The  condi- 
tion, especially  the  congenital  form,  may  exist  unsuspected 
until  found  at  the  autopsy,  death  being  the  result  of  some 
other  disease.  Great  enlargement  of  both  kidneys,  with 
hypertrophy  of  the  left  ventricle  and  increased  arterial  ten- 
sion, would  suggest  cystic  disease. 

Operative  interference  is  not  justifiable.  It  is  important 
to  remember  that  the  conglomerate  cystic  kidney  is  almost 
invariably  bilateral.  Osier  cites  an  instance  in  w^hich  one 
kidney  was  removed  and  the  patient  died  within  twenty-four 
hours  from  cystic  disease  of  the  other  kidney. 


CHAPTER  X. 

DISEASES  OF  THE  URINARY  TRACT  BELOW 
THE  KIDNEY  PROPER, 

The  diseases  of  the  urinary  tract  below  the  kidney 
proper  have  received  names  according  to  their  location  and 
their  duration.  They  are,  for  the  most  part,  inflammatory 
in  character,  and  may  be  either  acute  or  chronic.  In  a 
consideration  of  the  urine  of  all  such  diseases,  the  quantity 
of  albumin,  the  total  amount  of  urea,  and  the  character  of 
the  sediment  are  of  special  importance  for  purposes  of 
diagnosis. 

PYELITIS. 

This  is  an  inflammation  of  the  mucous  membrane  of  the 
pelvis  of  the  kidney  ;  it  may  be  either  acute  or  chronic. 

ACUTE  PYELITIS. 

An  acute  inflammation  of  the  pelvis  of  the  kidney  may 
be  either  mild  or  severe,  and  local  or  general.  Primary 
acute  pyelitis  is  not  of  common  occurrence,  but  is  usually 
found  to  exist  as  an  accompaniment  or  a  complication  of  an 
acute  disease  of  the  kidney  proper. 

Causes. — The  disease  is  usually  produced  in  one  of 
three  ways  :  (i)  By  the  extension  of  an  inflammatory 
process  downward  from  the  kidney;  (2)  by  the  upward 
extension  of  disease  of  the  bladder ;  (3)  by  irritants  con- 
fined within  the  pelvic  cavity  itself  An  acute  nephritis 
is  usually  accompanied  by  a  more  or  less  severe  acute 
pyelitis  (see  p.  295) — in  other  words,  the  irritant  that 
has  set  up  the  nephritis  has  also  had  its  irritating  influ- 
ence on  the  mucous  membrane  of  the  pelvis  by  extension 
downward.  Not  infrequently  an  acute  pyelitis  (together 
with  an  acute  nephritis)  follows  exposure  to  cold  and 
wet,  and  it  may  be  set   up  by  the   irritating  action  of  the 

331 


332  DISEASES  OF  THE  URINARY  TRACT. 

toxines  of  certain  acute  infectious  diseases,  such  as  typhoid 
fever,  scarlet  fever,  diphtheria,  and  septicemia.  A  gonor- 
rheal infection  of  the  lower  urinary  tract  may,  by  exten- 
sion, result  in  an  acute  pyelitis,  and  sometimes,  later,  an 
acute  nephritis.  When  an  acute  pyelitis  occurs  without 
an  accompanying  acute  nephritis  or  disease  of  the  lower 
urinary  passages,  it  is  almost  invariably  due  to  the  irritat- 
ing action  of  crystalline  elements  or  to  a  small  concretion 
within  the  pelvic  cavity.  If  due  to  a  concretion,  the  inflam- 
matory process  may  be  circumscribed.  Rarely,  the  pressure 
of  a  new  growth,  which  is  located  outside  of  the  urinary 
tract,  on  the  pelvis  of  the  kidney  results  in  an  acute  pyelitis. 

Prominent  Symptoms. — There  is  usually  more  or  less 
pain  referred  to  the  region  of  the  affected  kidney  or  kidneys, 
and  it  is  often  found  radiating  along  the  course  of  the  ureter 
toward  the  groin.  There  is  frequently  some  fever,  although, 
as  a  rule,  the  temperature  is  not  high.  The  disease  may, 
however,  be  ushered  in  by  a  chill  or  a  succession  of  rigors 
followed  by  a  high  temperature  for  a  day  or  two.  Hema- 
turia is  an  early  symptom,  and  usually  continues  for  several 
days.  The  patient  may  suffer  from  renal  colic,  caused  by 
the  marked  irritation  of  crystalline  elements  or  by  a  cal- 
culus or  blood-clot  obstructing  the  outflow  of  urine  through 
the  ureter.  Rarely,  a  pyonephrosis  results  from  obstruc- 
tion in  the  ureter.  Micturition  is  more  frequent  than 
normal.  The  symptoms  of  an  accompanying  acute  nephri- 
tis or  a  cystitis  are  often  sufficiently  prominent  to  entirely 
obscure  those  that  are  referable  to  the  pelvis  itself. 

Character  of  the  Urine. — The  urine  of  a  simple  acute 
pyelitis,  without  much  involvement  of  the  kidney  proper, 
usually  has  the  characteristics  of  a  fever  urine. 

Quantity. — Considerably  diminished — /.  e.,  from  400  to 
800  or  1000  c.c. 

Color. — High,  and  frequently  smoky,  sometimes  a  blood- 
red  color,  depending  upon  the  amount  and  character  of  the 
blood  present. 

Specific  Gravity. — This  is  generally  higher  than  normal 
— 1025  to  1030,  or  as  high  as  1035. 

Normal  Solids. — Absohitcly,  diminished  ;  relatively,  in- 
creased. 

Albumin. — The  quantity  of  albumin  is  variable,  but  in  a 
general  way  corresponds  to  the  amount  of  blood  and  pus 
present.     As  a  rule,  the  quantity  of  albumin  is  chiefly  rela- 


CHRONIC   PYELITIS.  333 

tive  to  the  amount  of  blood  rather  than  to  the  quantity 
of  pus  present.  The  quantity  usually  varies  between  a 
sliglit  trace  and  y^  oi  \  per  cent. 

Sediment. — Chiefly  normal  blood.  Numerous  small 
caudate  cells  from  the  superficial  layer  of  the  pelvis  of  the 
kidney.  Some  pus,  both  free  and  in  clumps.  There  are, 
frequently,  clumps  of  small,  medium,  or  large  round  cells 
from  the  calices  of  the  kidney.  Since  there  is  nearly  always 
some  extension  of  the  inflammatory  process  into  the  straight 
tubules,  a  few  (or  occasional)  granular  and  brown  granular 
casts  with  adherent  renal  cells  from  the  straight  tubules,  and 
abnormal  blood  will  be  found.  If  the  tubular  involvement 
is  marked,  the  number  of  casts  will  be  much  larger,  and  the 
general  characteristics  of  the  urine  will  approach  those  of 
an  acute  nephritis  complicated  by  an  acute  pyelitis.  The 
presence  of  crystals  or  crystalline  fragments  should  always 
be  noted,  for  they  may  be  the  cause  of  the  pyelitis,  or  may 
lead  to  the  diagnosis  of  a  calculus  and  the  probable  compo- 
sition of  the  same. 

An  acute  pyelitis  as  a  complication  of  an  acute  nephritis 
or  the  result  of  an  irritant  toxine  usually  disappears  with  the 
subsidence  of  the  primary  affection.  Sometimes  it  lasts 
only  a  few  days  and  then,  quite  suddenly,  the  urine  and 
sediment  bear  the  characteristics  of  a  chronic  pyelitis. 
When  the  disease  is  due  to  the  presence  of  a  concretion  or 
to  a  gonorrheal  infection,  it  very  soon  becomes  chronic,  and 
may  continue  for  months  or  years  as  a  chronic  pyelitis. 

CHRONIC  PYELITIS. 

-This  is  a  chronic  inflammation  of  the  mucous  membrane 
of  the  pelvis  of  the  kidney.  It  may  be  mild  or  severe,  and 
local  or  general. 

Causes. — A  chronic  pyelitis  is  induced  by  a  variety  of 
causes,  among  which  the  following  are  the  most  important : 
(i)  The  irritation  by  crystals  or  calculi — a  very  common 
cause.  (2)  Tuberculosis.  (3)  The  infectious  pyelitis  that 
develops  in  fevers,  in  which  an  acute  pyelitis  precedes  the 
chronic  inflammation.  (4)  Obstruction  to  the  outflow  of 
urine  through  the  ureter,  as  by  an  impacted  calculus,  blood- 
clot,  stricture  or  twist  of  the  ureter,  etc.  (5)  The  presence 
of  decomposing  urine,  following  pressure  upon  the  ureter 
by  tumors  located  outside  the  urinary  tract.  (6)  A  frequent 
cause  of  a  chronic  pyelitis  is  the  upward  extension  of  an 


334  DISEASES  OF  THE   URIXARY  TRACT. 

inflammation  of  the  bladder.  (7)  Obstruction  to  the  out- 
flow of  urine  by  a  tight  stricture  of  the  urethra,  a  very  nar- 
row prepuce,  or  tumor  of  the  bladder.     (8)  Movable  kidney. 

Prominent  Symptoms. — In  the  forms  of  chronic  pyelitis 
associated  with  the  acute  febrile  diseases  symptoms  may 
be  wanting.  There  may  be  more  or  less  pain  in  the  region 
of  the  affected  organ.  If,  at  any  time,  there  is  retention  of 
the  pus  as  the  result  of  obstruction  in  the  ureter  or  bladder, 
chills  followed  by  fever,  sweats,  and  sometimes  renal  colic 
ensue.  Such  symptoms  rapidly  disappear  following  an 
evacuation  of  the  pus,  but  spontaneous  evacuation  of  the 
pus  cavity  (renal  pelvis)  may  not  take  place  ;  under  these 
circumstances  a  true  pyonephrosis  results.  Aside  from 
twists  of  the  ureter,  perhaps  the  most  common  cause  of 
frequent  attacks  of  retention  of  pus,  followed  in  a  few  days 
by  evacuation  of  the  pus  cavity,  is  the  presence  of  calculi 
in  the  renal  pelvis,  the  obstruction  being  removed  b)'  a 
change  of  position  or  other  means.  A  pyonephrosis  with 
its  attending  symptoms  is  not  an  uncommon  outcome  of  a 
chronic  pyelitis. 

Character  of  the  Urine. — The  urine  has  the  general 
characteristics  of  one  of  a  chronic  disease. 

Quantity. — Usually,  less  than  normal — about  1200  c.c. 

Color. — Pale.  The  urine  is  generally  ver\- turbid,  due  to 
the  pus  in  suspension. 

Reaction. — Usually,  faintly  acid.  The  urine  readily  be- 
comes alkaline  upon  standing. 

Specific  Gravity. — This  is  below  the  normal — loio  to 
1015. 

Normal  Solids, — Both  absolutely  and  relatively,  dimin- 
ished. The  absolute  quantity  of  urea  will  usually  be  found 
to  vary  between  15  and  25  grams  ;  the  extent  of  the  dimi- 
nution will  depend  upon  the  metabolism. 

Albumin. — This  is  relative  chiefly  to  the  amount  of 
blood  and  pus  present ;  if  the  kidney  proper  is  only  slightly 
involved,  the  albumin  will  generally  var}'  between  a  very 
sligJit  trace  and  a  large  trace. 

Sediment. — Chiefly  degenerated  pus,  both  free  and  in 
clumps  ;  many  small  round  cells,  some  in  the  clumps  of 
pus  ;  a  few  blood  globules.  In  most  cases  there  is  more 
or  less  involvement  of  the  straight  tubules  of  the  kidney  ;  but 
renal  casts  are  often  difficult  of  detection  in  the  sediment, 
owing  to  the  presence   of  the  pus  which  obscures  them. 


CALCULOUS  PYELITIS.  335 

In  a  chronic  pyelitis  the  casts  present,  are  usually  of  large 
diameter,  and  they  may  have  leucocytes  adherent  to  them, 
or  there  may  be  true  pus  casts. 

A  careful  search  should  always  be  made  for  crystals  or 
crystalline  fragments,  and  when  present  the  diagnosis  of  a 
calculous  pyelitis  is  rendered  probable.  On  the  other  hand, 
a  concretion  may  exist  in  the  renal  pelvis  without  the  pres- 
ence of  any  formed  crystals,  or  crystalline  elements,  in  the 
sediment.  Great  care  should  be  taken  not  to  mistake  ex- 
traneous particles  of  dust,  pieces  of  broken  glass,  etc.,  for 
fragments  of  a  calculus. 

The  urinary  sediment  should  in  all  doubtful  cases  be 
examined  for  tubercle  bacilli,  for  it  is  only  by  this  means 
that  a  tubercular  pyelitis  can  be  eliminated. 

The  diagnosis  of  a  new  growth  involving  the  pelvis  of 
the  kidney  is  very  difficult  from  the  urine  alone.  Rarely, 
the  presence  of  an  unusual  number  of  cellular  elements 
leads  to  such  a  diagnosis,  but  such  inferences  should  be 
well  guarded  by  clinical  signs  and  symptoms. 

Duration  and  Prognosis. — A  chronic  pyelitis  usually 
disappears  with  the  removal  of  the  cause,  if  su^h  is  possible. 
If  due  to  tuberculosis  or  a  new  growth  of  the  kidney  and 
its  pelvis,  surgical  interference  is  usually  necessary. 

There  is  constant  danger  of  disease  of  the  healthy  kidney, 
and  when  it  occurs,  there  is,  unfortunately,  little  that  can  be 
done  to  relieve  the  condition.  The  disease  in  a  mild  form 
may  continue  for  years  without  causing,  in  itself,  much  suf- 
fering. This  is  especially  the  case  when  the  disease  is  caused 
by  accidental  twists  of  the  ureter  as  in  floating  kidney, 
in  which  instance  the  urine  is  retained  in  the  renal  pelvis 
until  a  time  when  the  pressure  of  the  retained  fluid  becomes 
sufficient  to  force  its  escape,  or  until  the  kidney  regains  its 
normal  position  by  a  sudden  change  of  position  of  the 
patient,  or  until  it  is  replaced  by  surgical  operation.  When 
the  kidney  is  stitched  into  position,  the  chronic  pyelitis 
usually  subsides  in  a  short  time  ;  otherwise  the  disease  may 
continue  in  a  mild  form  as  long  as  these  temporary  twists 
of  the  ureter  occur. 

CALCULOUS  PYELITIS. 

Although  this  subject  has  been  considered  in  connection 
with  an  acute  and  chronic  pyelitis,  it  deserves  special  atten- 
tion because  of  its  importance. 


33.6  DISEASES  OF  THE  URINARY  TRACT. 

Calculi  that  cause  pyelitis  may  be  large  or  small,  and 
may  be  free  in  the  pelvis  or  become  encysted.  They 
often  have  projections  that  extend  up  into  the  calices  and 
sometimes  into  the  straight  tubules ;  the  tubules  thus 
obstructed  become  dilated  by  the  purulent  urine,  and 
often  result  in  abscesses.  When  the  pressure  of  the  fluid 
in  the  abscess  sac  becomes  sufficient  to  dislodge  the 
obstructing  calculus,  the  urine  suddenly  contains  a  large 
amount  of  pus,  which  is  almost  invariably  of  a  greenish 
color.  Sometimes  there  is  a  gradual  leakage  of  pus  about 
the  seat  of  the  obstruction,  and  not  infrequently  the  abscess 
connects  with  one  or  more  tubules,  so  that  the  urine  con- 
stantly contains  pus,  and  often  in  enormous  quantities.  The 
author  has  recently  seen  a  case  of  multiple  abscess  of  the 
kidney  due  to  a  large  calculus  in  the  pelvis,  in  which  the 
pus  sacs  apparently  had  a  common  opening  from  which  an 
enormous  amount  of  pus  was  discharged — nearly  one-fourth 
of  the  twenty-four-hour  urine  being  thick  greenish  pus. 

In  calculous  pyelitis  there  may  be  only  slight  tubidity  of 
the  mucous  membrane,  such  a  condition  being  sometimes 
called  catarrhal  pyelitis.  More  commonly,  the  mucous  sur- 
face is  roughened,  grayish  in  color,  and  thick.  Under  these 
circumstances  there  are  almost  always  more  or  less  dilata- 
tion of  the  calices  and  flattening  of  the  papillae.  Follow- 
ing this  condition  there  may  be  (i)  extension  of  the  suppu- 
rative process  to  the  kidney  itself,  forming  a  pyelonephritis. 
(2)  A  gradual  dilatation  of  the  calices  with  atrophy  of  the 
kidney  substance,  and,  finally,  the  production  of  the  condi- 
tion of  pyonephrosis  in  which  the  entire  organ  is  repre- 
sented by  a  sac  of  pus  with  or  without  a  thin  shell  of  renal 
tissue.  (3)  After  the  kidney  structure  has  been  destroyed 
by  suppuration,  if  the  obstruction  at  the  orifice  of  the  pelvis 
persists,  the  fluid  portions  may  be  absorbed,  and  the  pus 
become  inspissated,  so  that  the  organ  is  represented  by  a 
series  of  sacculi  containing  grayish  pap-like  masses,  which 
have  become  impregnated  with  lime-salts. 

Prominent  Symptoms. — The  symptoms  are,  for  the 
most  part,  the  same  as  those  in  chronic  pyelitis.  There  may 
be  pain  in  the  back  or  there  may  be  tenderness  on  deep 
pressure  on  the  affected  side.  Before  the  condition  of 
pyuria  is  established,  besides  the  attacks  of  pain,  there  may 
be  rigors,  high  fever,  and  sweats.  Pain  is  often  increased 
by  exercise, — walking    or    riding, — but    not    in    all    cases. 


HYDRONEPHROSIS.  337 

Coincident  with  the  retention  of  pus,  a  tumor  may  be  felt 
on  the  affected  side.  The  general  condition  of  the  patient 
usually  indicates  prolonged  suppuration.  Occasionally, 
nervous  symptoms,  which  may  be  associated  with  dyspnea, 
supervene  ;  or  the  termination  may  be  by  coma.  These 
nervous  phenomena  have  been  attributed  to  the  absorption 
of  the  decomposed  materials  from  the  seat  of  the  disease. 

Character  of  the  Urine. — The  urine  generally  has  the 
characteristics  of  an  acute  or  a  chronic  pyelitis.  The  most 
predominant  element  in  the  sediment  is  the  pus,  which  is 
often  present  in  large  quantity.  There  is  usually  more  or 
less  blood,  and  sometimes  it  is  present  in  considerable  quan- 
tity. The  sediment  may,  or  may  not,  contain  crystalline 
elements  or  concretions ;  the  mere  absence  of  cr}^stals 
would  not  be  sufficient  ground  for  excluding  the  condition 
of  calculous  pyelitis. 

Usually,  the  other  (unaffected)  kidney  is  more  or  less 
congested  as  a  result  of  the  elimination  of  toxines  from  the 
diseased  organ.  This  is  especially  the  case  in  chronic  pye- 
litis or  abscess  of  the  kidney  due  to  a  stone,  but  it  is  often 
very  difficult  to  find  renal  casts  in  the  presence  of  so  much 
pus. 

Diagnosis.  —  Between  the  tuberculous  and  calculous 
forms  of  pyelitis  it  may  be  difficult  or  impossible  to  distin- 
guish, except  by  the  detection  of  tubercle  bacilli  in  the 
urinary  sediment.  The  examination  for  tubercle  bacilli 
should  be  made  systematically  in  all  suspicious  cases,  and 
if  not  found  by  the  microscope,  guinea-pigs  should  be  in- 
oculated with  a  portion  of  the  sediment. 


HYDRONEPHROSIS. 

This  is  a  condition  due  to  an  obstruction  in  the  ureter  and 
the  retention  of  7io7iptirident  urine  in  the  pelvis  of  the  kidney. 
If  the  obstruction  continues,  the  pelvis  of  the  kidney  be- 
comes extremely  dilated,  and  as  a  result  of  the  back  pres- 
sure there  is  a  marked  dilatation  of  the  straight  tubules,  and 
then  the  smaller  tubules.  Finally,  the  kidney  and  its  pelvis 
are  converted  into  a  sac,  which  may  be  of  sufficient  size  to 
produce  a  tumor  on  the  affected  side.  The  kidney  soon 
loses  its  function  after  the  urine  begins  to  back  up  into  the 
small  tubules,  and,  finally,  the  entire  work  of  secretion  and 
excretion  is  thrown  on  the  other  kidney. 

22 


338  DISEASES  OF  THE  URINARY  TRACT. 

About  from  thirty-five  to  forty  per  cent,  of  these  cases  are 
congenital,  the  remainder  may  be  acquired.  The  congenital 
causes  comprise  twists  of  the  ureter  upon  its  axis,  undue 
obliquity  of  the  ureteral  opening  into  the  bladder,  redupli- 
cation, valve-like  folds  of  the  mucous  membrane  of  the  ure- 
ter, and  imperforate  ureter.  The  acquired  causes  are  (i)  an 
impaction  of  a  calculus  ;  (2)  a  blood-clot  in  the  ureter;  (3) 
stricture  of  the  ureter,  especially  following  traumatism  ;  (4) 
twist  of  the  ureter,  particularly  in  case  of  "  floating  kidney," 
and  if  due  to  this  cause,  the  condition  usually  continues  until 
the  pressure  becomes  sufficient  to  force  an  opening  and 
allow  the  fluid  to  escape  (intermittent  hydronephrosis)  ;  (5) 
new  growth  in  the  pelvis  or  ureter,  or  one  outside  of  the 
urinary  tract,  causing  marked  pressure  on  the  ureter. 

Prominent  Symptoms. — A  dull,  aching  pain  is  usually 
present  in  the  renal  region.  A  tumor  is  present  in  most 
cases,  gradually  encroaching  on  the  median  line  and  down- 
ward toward  the  iliac  fossa.  A  sudden  diminution  in  the 
size  of  the  tumor  coincident  with  the  elimination  of  an 
unusual  quantity  of  nonpurulent  urine,  may  be  considered 
diagnostic.  Vomiting  sometimes  occurs  during  these  periods 
of  retention,  and  occasionally  a  urinous  odor  may  be  observed 
in  the  perspiration  at  such  times,  especially  if  both  kidneys 
are  involved.  Constipation  is  a  frequent  result  of  pressure 
upon  the  colon  ;  more  rarely,  diarrhea  maybe  present  from 
the  same  cause.  As  long  as  the  hydronephrosis  is  single 
and  the  remaining  kidney  healthy,  there  is  usually  an 
absence  of  uremic  symptoms.  Enlargement  of  the  unaf- 
fected kidney  may  compensate  for  the  defective  elimination. 
Hypertrophy  of  the  left  side  of  the  heart  usually  follows. 

Character  of  the  Urine. — Owing  to  the  virtual  loss  of 
function  of  the  affected  kidney,  the  entire  work  of  elimina- 
tion is  thrown  on  the  other  kidney  and,  as  a  result,  it  is 
common  to  find  evidence  of  more  or  less  active  congestion 
of  the  unaffected  organ.  (See  Active  Hyperemia.)  The 
quantity  of  urine  is  generally  diminished  ;  the  normal  solids 
are  absolutely  diminished,  although  not  to  a  marked  degree  ; 
and  there  is  usually  albumin,  varying  between  the  slightest 
possible  trace  and  a  trace.  The  sediment  usually  contains 
an  occasional  (or  {q.\\^  hyaline,  granular,  and  brown  granu- 
lar casts,  some  of  which  have  renal  cells  and  a  little  abnor- 
mal blood  adherent ;  and  a  {q.\n  free  renal  cells  and  blood 
globules. 


PYONEPHROSIS.  339 

In  rare  instances  the  urine  may  be  perfectly  normal. 

The  fluid  in  the  Jiydroncplirotic  sac  is  usually  of  a  pale 
color,  of  low  specific  gravity,  and  contains  only  small 
amounts  of  the  normal  urinary  constituents,  notably  urea 
and  uric  acid.  Albumin  is  generally  present,  the  quantity 
being  in  the  neighborhood  of  a  trace.  The  sediment  wswdWy 
consists  of  a  few  blood  globules,  cells  from  the  pelvis  and 
tubules  of  the  kidney,  and  a  iQ.\N  casts  of  small  diameter 
from  the  higher  tubules.  There  is  no  pus,  or,  at  the  most, 
only  an  occasional  leucocyte. 

The  outlook  in  hydronephrosis  depends  upon  the  cause. 
When  unilateral,  the  condition  may  never  produce  serious 
trouble,  and  the  intermittent  forms  may  persist  for  years  and 
finally  disappear.  Occasionally,  the  cyst  ruptures  into  the 
peritoneum,  more  rarely  through  the  diaphragm  into  the 
pleural  cavity  and  lung.  The  sac  may  discharge  spontane- 
ously through  the  ureter  and  the  fluid  never  reaccumulate, 
or  the  condition  may  change  to  one  of  pyonephrosis. 


PYONEPHROSIS. 

This  condition  is  the  result  of  an  obstruction  to  the  out- 
flow of  urine  through  the  ureter,  and  the  retention  of  piirn- 
lent  urine  in  the  renal  pelvis.  It  usually  follows  a  pre- 
existing acute  or  chronic  pyelitis,  although  it  may  exist 
primarily  as  a  hydronephrosis,  and  later  become  a  pyo- 
nephrosis as  a  result  of  the  inflammatory  process  set  up  by 
chemic  or  mechanical  irritants  in  the  pelvis — notably  crys- 
talline elements  or  a  calculus. 

"The  destruction  of  the  kidney  is  sometimes  very  rapid, 
because  of  the  retained  pus-containing  fluid  and  the  ex- 
tension of  the  inflammatory  process  to  various  parts  of  the 
kidney  proper.  As  in  hydronephrosis,  the  back  pressure 
of  the  retained  fluid  results,  first,  in  a  marked  dilatation  of 
the  renal  pelvis  ;  next,  the  straight  tubules  ;  then,  the  smaller 
tubes,  which  become  atrophied  and  lose  their  function  ;  and, 
finally,  the  disorganized  kidney  and  its  pelvis  constitute  a 
large  pus  sac. 

Causes. — Any  of  the  causes  ascribed  to  a  hydronephrosis 
may  produce  a  pyonephrosis  by  partially  or  entirely  oc- 
cluding the  ureter,  if  a  pyogenic  organism  be  present. 
Of  these  the  most  common  are  impacted  calculus,  twist 
of  the    ureter    in    case    of    "floating    kidney,"    and   trau- 


340  DISEASES  OF  THE  URINARY  TRACT. 

matic  or  inflammatory  stricture  of  the  ureter.  Marked  pres- 
sure on  the  ureter  or  the  pelvis  of  the  kidney  by  new  growths 
that  are  situated  outside  of  the  urinary  tract  may  produce 
this  condition. 

Prominent  Symptoms. — The  most  prominent  symptoms 
of  pyonephrosis  comprise  pyuria  with  constitutional  symp- 
toms, such  as  chills,  irregular  temperature,  emaciation, 
anemia,  and  prostration.  If  there  is  a  tumor,  it  may  be 
elastic  and  fluctuating,  or  hard,  and  extend  both  forward 
and  downward.  Pain  is  present,  varying  with  the  size  of 
the  tumor  and  degree  of  fluctuation  ;  it  often  appears  in 
paroxysms  of  intensity — renal  colic.  Pressure  over  the 
anterior  of  the  tumor  greatly  increases  the  pain,  or  causes 
it  if  not  present  before.  On  the  other  hand,  lateral  pressure 
may  relieve  the  pain  when  present.  The  bowels  are  usually 
disturbed,  constipation  or  diarrhea  being  frequent.  The 
sudden  appearance  of  a  purulent  urine  that  has  previously 
been  clear  and  free  from  pus  is  often  of  great  diagnostic 
value. 

Character  of  the  Urine. — If  the  pyonephrosis  is  uni- 
lateral and  the  occlusion  of  the  ureter  on  the  affected  side  is 
complete,  the  urine  usually  shows  the  existence  of  a  more  or 
less  severe  active  hyperemia  of  the  unaffected  kidney.  This 
is  undoubtedly  due  partly  to  the  absorption  of  toxic  prod- 
ucts from  the  diseased  kidney,  and  partly  to  the  extra  work 
of  elimination.  The  urine  will  be  free  from  pus  and  other 
evidences  of  a  pyonephrosis,  so  that  the  diagnosis  of  this 
condition  can  only  be  made  from  the  physical  examination 
and  the  clinical  symptoms. 

If  by  any  means  the  obstruction  in  the  ureter  be  re- 
moved, the  urine  will  suddenly  become  veiy  turbid,  and 
when  it  settles  will  contain  a  very  abundant  sediment  hav- 
ing a  decidedly  greenish  tint.  On  microscopic  examination 
this  sediment  will  be  found  to  consist  of  a  large  quantity 
of  degenerated  and  disintegrated  pus,  accompanied  by  an 
abundance  of  small  round  cells.  There  may  be  a  small 
amount  of  blood  in  this  sediment,  but  usually  blood- 
corpuscles  are  difficult  to  find — or,  more  properly,  difficult 
to  recognize — in  the  presence  of  so  much  pus. 

The  odor  of  the  urine  containing  the  pus  is  generally 
very  offensive,  and  sometimes  the  reaction  is  alkaline. 

The  quantity  of  albumin  is  usually  large, —  y%  to  /^  of  i 
per  cent,  or  more, — and  very  often  the  albumin  is  accom- 


URETERITIS.  341 

panied  by  an  abundance  of  globulin.  The  author  has  met 
with  one  case  in  which  the  quantity  of  globulin  equaled 
that  of  the  albumin.  From  a  diagnostic  point  of  view  the 
other  characteristics  of  the  urine  are  not  especially  significant. 

It  is  often  necessary  to  remove  the  diseased  kidney  in 
order  to  save  the  life  of  the  patient.  The  pus  sac  thus 
removed  usually  contains  very  little,  if  any,  fluid  material, 
but,  instead,  a  thick,  putty-like  or  cheesy  mass  of  inspis- 
sated pus,  the  liquid  portion  having  been  previously  ab- 
sorbed. This  putt}'-like  substance  may  contain  a  deposit 
of  lime-salts. 

A  pyonephrosis  is  always  attended  with  danger  to  life. 
Perforation  into  the  peritoneal  or  pleural  cavities  may 
occur,  or  the  patient  may  be  worn  out  by  the  hectic  fever, 
or  amyloid  disease  may  develop. 

URETERITIS. 

An  inflammation  of  the  mucous  membrane  of  the  ureter 
may  be  acute  or  chronic.  The  inflammatory  process  may 
be  local  or  general,  according  to  the  cause. 

A  diagnosis  of  this  condition  from  the  urine  alone  is 
practically  impossible,  especially  if  the  urine  is  voided  in 
the  natural  way.  Since  the  advent  of  catheterization  of  the 
female  ureters,  exceptional  opportunities  have  been  afforded 
for  studying  diseases  of  this  tract,  and  some  instructive 
observations  have  been  made. 

Causes. — This  inflammatory  condition  may  be  a  part  of 
an  acute  pyelitis  or  an  acute  cystitis,  by  extension.  It  is 
probably  more  frequent  in  connection  with  an  acute  pye- 
litis, and  often  due  to  the  same  causes.  (See  p.  331.) 
Aside  from  an  inflammatory  process  due  to  exposure  to 
cold  and  wet,  perhaps  the  most  common  cause  is  the  pas- 
sage of  calculi  or  microscopic  crystals  of  uric  acid  or  cal- 
cium oxalate.  If  the  calculus  can  not  be  forced  through 
the  ureter,  it  first  produces  a  marked  acute  ureteritis  and 
later  a  chronic  inflammation  at  its  lodging  point,  which  is 
frequently  at  the  place  where  the  ureter  crosses  the  brim  of 
the  pelvis.  The  microscopic  crystals  often  produce  an  irri- 
tation or  inflammation  of  the  mucous  membrane  through- 
out the  entire  length  of  the  tube.  Like  an  acute  pyelitis, 
the  acute  process  in  the  ureter  soon  becomes  chronic.  The 
inflammation   may   have    the    characteristics   of    a  chronic 


342  DISEASES  OF  THE   URINARY  TRACT. 

ureteritis  from  the  beginning,  as  in  tubercular  ulcerations, 
or  a  gradual  extension  upward  of  a  chronic  inflammation 
of  the  bladder.  The  pressure  on  the  ureter  by  new  growths 
located  outside  of  the  urinary  tract,  twists,  and  strictures  of 
the  ureter  often  produce  more  or  less  inflammation. 

Symptoms. — The  most  prominent  clinical  feature  is  the 
paroxysmal  sharp  pain — renal  colic — that  starts  in  the 
region  of  the  kidney,  follows  down  the  line  of  the  ureter 
into  the  testicle,  and  along  the  inner  side  of  the  thigh. 
During  the  paroxysm  of  pain  there  is  usually  nausea  and 
vomiting,  marked  prostration,  and  sometimes  a  little  fever. 
(See  Renal  Calculus.)  On  bimanual  examination  the 
thickened  ureter  or  impacted  calculus  can,  occasionally, 
be  felt  through  the  abdominal  wall. 

Character  of  the  Urine. — The  urine  usually  has  the 
characteristics  of  the  inflammatory  process  above  or  below 
the  ureter — acute  or  chronic  pyelitis,  and  acute  or  chronic 
cystitis.  The  diagnosis  of  a  simple  ureteritis,  if  such  exists 
without  a  pyelitis  or  cystitis,  can  only  rarely  be  made  from  the 
urine  alone  ;  even  then  it  is  ver}'  difficult  to  distinguish  it  from 
an  irritation  or  acute  inflammation  of  the  pelvis  of  the  kid- 
ney. In  a  simple  ureteritis  due  to  an  impacted  calculus  the 
urine  usually  has  a  high  color,  strongly  acid  reaction,  and 
high  specific  gravity.  The  quantity  of  albumin  commonly 
varies  with  the  amount  of  blood.  The  sediment  frequently 
contains  more  or  less  blood,  and  sometimes  the  blood  is 
present  in  abundance.  There  are  usually  small  caudate 
and  spindle  cells  from  the  ureter,  and  a  few  (or  numerous) 
leucocytes. 

Catheterization  of  the  ureters  may  lead  to  the  diagnosis 
of  ureteritis,  stricture  of  the  ureter,  or  the  presence  of  a  cal- 
culus in  the  ureter.  The  history  of  renal  colic,  or  of  more 
or  less  continuous  pain  in  the  region  of  the  ureter,  is  of 
importance  in  the  diagnosis. 


CYSTITIS. 

This  is  an  inflammation  of  the  mucous  membrane  of  the 
bladder ;  it  may  be  either  acute  or  chronic. 

ACUTE  CYSTITIS. 

Causes. — One  of  the  most  common  causes  of  this  disease 
is  an  infection  with  micro-organisms,  such  as  the  gonococ- 


ACUTE  CYSTITIS.  343 

cus  in  cases  of  backward  extension  of  a  gonorrheal  ure- 
thritis ;  with  the  pyogenic  staphylococci  and  other  forms  of 
pyogenic  bacteria  that  have  been  introduced  into  the  bladder 
by  means  of  an  unclean  catheter  ;  and  with  the  tubercle 
bacillus.  It  may  result  from  an  acute  prostatitis  ;  from  in- 
jury, as  with  the  rough  use  of  sounds  ;  from  extensive  ure- 
thral stricture  ;  from  foreign  bodies,  such  as  calculi  ;  from 
drugs,  such  as  cantharides  and  copaiba ;  and  from  new 
growths.  An  acute  cystitis  is  not  uncommonly  seen  fol- 
lowing exposure  to  cold  and  wet,  sexual  .excesses,  and 
simple  acute  retention  of  urine.  An  acute  inflammation 
of  the  bladder  is  a  frequent  complication  of  acute  infec- 
tious diseases,  notably  typhoid  fever,  in  which  case  it  is 
probably  the  direct  result  of  the  action  of  the  typhoid 
bacillus. 

In  the  mild  cases  of  acute  cystitis  the  vesical  mucous 
membrane  is  congested,  thickened,  and  swollen,  and  the 
epithelium  becomes  detached  in  places,  leaving  abraded  sur- 
faces. In  the  severe  forms  the  bladder  becomes  lined  with 
a  tough,  tenacious  layer  of  mucin  (?)  ;  there  may  be  ulcera- 
tions and  sloughing.  The  submucous  connective  tissue  is, 
in  some  cases,  infiltrated  with  pus,  and  hemorrhagic  areas 
are  not  uncommon. 

Prominent  Symptoms. — One  of  the  first  symptoms  is 
increased  frequency  of  micturition,  which  usually  becomes 
more  and  more  prominent,  only  a  very  small  quantity  of 
urine  being  voided  at  each  effort  at  urination.  Tenesmus  is 
frequently  very  severe  ;  the  patient  will  often  lean  over  the 
vessel  or  urinal,  quivering  with  the  muscular  effort,  without 
relief  to  the  distressing  and  very  urgent  desire.  The  pain, 
which  is  likewise  extreme,  may  be  referred  to  the  neck  of 
the  bladder,  to  the  perineum,  to  the  glans  penis,  or  to  the 
hypogastrium,  and  may  radiate  into  the  loins  or  down  the 
thighs.  There  is  frequently  marked  constitutional  disturb- 
ance with  more  or  less  elevation  of  temperature,  although  in 
some  cases  the  general  disturbance  is  slight  in  comparison 
with  the  intensity  of  the  local  symptoms. 

Character  of  the  Urine.— Quantity. — The  twenty-four- 
hour  quantity  of  urine  is  usually  small,  varying  from  500  to 
800  or  1000  c.c. 

Color. — Bloody  or  smoky,  depending  upon  the  amount 
and  character  of  the  blood  present. 

Reaction. — Strongly  acid. 


344  DISEASES  OF  THE  URINARY  TRACT. 

Specific  Gravity. — Early  in  the  disease  the  specific 
gravity  is  usually  high — 1025  to  1030;  later,  it  is  normal 
or  slightly  diminished — 1015  to  1022. 

Normal  Solids. — Relatively,  increased  ;  but  absolutely, 
more  or  less  diminished,  depending  upon  the  amount  of 
systemic  disturbance  set  up  by  the  disease. 

Albumin. — The  quantity  of  albumin  is  variable,  but  in 
a  general  way  it  is  relative  to  the  amount  of  blood  and  pus 
in  the  urine.  It  is  not  uncommon  for  the  quantity  of  albu- 
min to  reach  or  even  exceed  y^  of  i  per  cent.,  but  usually 
it  is  less  than  this  figure. 

Sediment. — The  sediment,  which  is  generally  abundant, 
consists  chiefly  of  normal  blood  ;  considerable  pus,  some  in 
clumps,  and  a  large  amount  of  squamous  epithelium. 
Numerous  small  round  cells,  perhaps  some  of  them  fatty, 
may  be  found. 

CHRONIC  CYSTITIS. 

Causes. — A  chronic  cystitis  may  result  from  an  acute 
cystitis.  In  some  instances  the  changes  taking  place  in  the 
mucous  membrane  of  the  bladder  are  so  sliijht  and  fjradual 
that  a  chronic  process  results  apparently  without  a  preexist- 
ing acute  stage.  In  general,  the  same  causes  that  have 
been  attributed  to  an  acute  inflammation  of  the  bladder  may 
be  looked  for  to  explain  the  presence  of  a  chronic  cystitis. 
Among  these  causes  are  to  be  borne  in  mind  infection 
by  micro-organisms,  as  following  the  introduction  of  insuf- 
ficiently purified  and  disinfected  catheters  or  bougies,  or 
when  the  instrument  carries  into  the  bladder  pus  and  bacte- 
ria from  an  ulcerating  surface  or  a  pus  pocket  in  the  urethra 
(stricture).  A  very  frequent  cause  of  this  form  of  cystitis 
is  the  enlarged  prostate.  Owing  to  the  inability  of  the 
patient  to  completely  empty  his  bladder,  the  residual  urine 
sooner  or  later  decomposes  by  the  rapid  development  of 
bacteria,  and  a  general  cystitis  results.  In  a  similar  manner 
many  cases  of  cystitis  arise  in  patients  with  nervous  disease, 
who  have  paralysis  of  the  bladder,  as  in  paraplegia  ;  also 
in  persons  who  are  severely  ill  and  stupid  from  some  acute 
disease,  such  as  typhoid  fever.  In  the  acute  infectious  dis- 
eases a  chronic  cystitis  may  appear,  either  as  the  result  of 
frequent  catheterization,  or  by  the  action  of  the  bacteria 
causing  the  disease. 

In  cases  of  vesical  calculus   vesical  tuberculosis,  and  new 


CHRONIC  CYSTITIS.  345 

growths  of  the  bladder,  a  chronic  cystitis  is  probably  more 
commonly  seen  than  an  acute  cystitis,  since  the  disturbance 
by  these  agencies  is  at  first  slight.  The  subsequent  changes, 
which  are  often  very  gradual,  become  more  pronounced, 
and  finally  a  well-marked  chronic  inflammatory  process  is 
apparent. 

In  women  the  agents  of  inflammation  may  quite  easily 
enter  the  bladder  from  the  vagina  through  the  short  female 
urethra  ;  thus  arise  the  frequent  cases  of  cystitis  in  childbed 
(usually  an  acute  cystitis).  Communications  may  develop 
between  the  bladder  and  certain  neighboring  organs,  such 
as  vesicorectal  or  vesicovaginal  fistulae,  by  which,  again, 
access  to  the  bladder  is  open  to  the  agents  of  inflammation. 

The  pathologic  changes  in  the  wall  of  the  bladder  may 
result  in  atony  or  atrophy,  with  thinning  of  the  mucous 
membrane,  fatty  degeneration  of  the  muscular  fibers  almost 
to  the  point  of  disappearance,  and  great  distention  of  the 
organ.  Again,  they  may  be  followed  by  hypertrophy  of 
the  muscular  coat,  the  fibers  forming  ridges  or  fasciculi 
standing  out  in  the  interior  of  the  bladder  and  separated  by 
lozenge -shaped  spaces,  the  organ  itself  being  contracted  so 
that  its  cavity  can  contain  but  a  few  cubic  centimeters  of 
fluid.  Sometimes  between  these  muscular  bars  pouches  of 
mucous  membrane  protrude,  forming  distinct  sacculi  com- 
municating with  the  interior  of  the  bladder  by  narrow 
mouths  and  remaining  permanently ;  occasionally,  they 
contain  calculi.  In  chronic  cystitis  of  long  standing  the 
mucous  membrane  often  takes  on  a  slaty,  grayish-black 
color  as  a  result  of  hemorrhages.  The  incrustation  of  the 
mucous  membrane  with  urinary  salts,  especially  with  am- 
monio-magnesium  phosphate,  is  also  frequently  found  in  the 
chronic  form  of  this  disease. 

Prominent  Symptoms. — The  symptoms  of  an  acute 
cystitis  are  present  in  a  modified  form.  Micturition  is  not 
so  frequent ;  tenesmus  is  much  less  or  is  absent  (in  mild 
cases) ;  pain  is  usually  very  slight,  and  in  mild  cases  it  may 
be  absent ;  the  constitutional  symptoms  are  comparatively 
slight,  and  become  marked  only  when  renal  changes  have 
occurred  or  when  a  general  toxemia  has  followed  the 
absorption  of  the  products  of  urinary  decomposition. 

Character  of  the  Urine. — Quantity. — The  twenty-four- 
hour  quantity  of  urine  is  usually  only  moderately  diminished 
— /.  c,  800  to  1400  c.c. 


346  DISEASES  OF  THE   URINARY  TRACT. 

Color. — Generally  pale,  but  it  may  be  normal  in  color  ; 
it  may,  however,  be  tinted  with  blood  to  a  greater  or  less 
extent.  The  freshly  passed  urine  is  generally  turbid,  due  to 
the  presence  of  pus  and  epithelium  and  an  abundance  of 
bacteria. 

Reaction. — Frequently  alkaline,  but  it  may  be  acid  and 
sometimes  it  is  strongly  acid,  especially  in  the  early  stages 
of  the  disease.  The  reaction  varies  according  to  the  pres- 
ence or  absence  of  urea-decomposing  organisms. 

Specific  Gravity. — This  varies  usually  between  ioi2 
and  I020  ;  average  about  1015. 

Normal  Solids. — Both  relatively  and  absolutely,  dimin- 
ished. 

Albumin. — This  varies  between  the  slightest  possible  trace 
(mild  cases)  and  ^  of  i  per  cent,  (severer  forms).  It  is 
usually  directly  dependent  upon  the  amount  of  pus  and 
blood  present. 

Sediment. — Abundant.  If  the  urine  be  acid,  the  sedi- 
ment will  consist  chiefly  of  pus  and  small  round  cells  ;  con- 
siderable squamous  epithelium,  and  generally  a  small 
(sometimes  a  considerable)  amount  of  blood.  If  the  urine 
be  alkaline, — ammoniacal, — the  sediment  will  settle  in  a 
viscid,  sticky  mass,  which  consists  mostly  of  decomposed 
pus,  amorphous  phosphates,  crystals  of  triple  phosphate, 
and  often  crystals  of  ammonium  urate.  The  pus  corpuscles 
may  be  so  embedded  in  the  mucin-like  substance  and  so 
changed  as  to  entirely  lose  their  characteristic  appearance. 

There  can  be  no  doubt  that  decomposing  alkaline  urine 
acts  as  a  chemic  irritant  to  the  mucous  membrane  of  the 
bladder  ;  hence,  cases  of  mild  cystitis  often  become  inten- 
sified by  the  irritation  of  the  ammonia  salts  that  are  formed. 

TUBERCULOSIS  OF  THE  BLADDER. 

Tuberculosis  of  the  bladder  is  not  an  uncommon  condi- 
tion. The  existence  of  a  chronic  inflammation  of  the  blad- 
der, in  the  absence  of  tangible  evidences  of  infection  from 
gonorrhea,  chronic  obstruction,  or  by  instrumentation, 
should  always  leave  a  suspicion  of  the  tubercular  nature  of 
the  affection.  The  two  places  in  which  tuberculosis  of  the 
bladder  is  most  likely  to  commence  are  the  trigone  and 
ureteral  orifices,  the  latter  being  the  more  common.  The 
tubercular  process  begins  with  the  formation  of  typical  gray 


TUBERCULOSIS  OF  THE  BLADDER.  347 

nodules  in  the  mucous  membrane  ;  these  nodules  become 
confluent,  caseate,  soften,  and  finally  produce  ulceration. 
In  more  acute  cases  the  disease  leads  to  diffuse  cheesy  infil- 
tration and  general  ulceration. 

Vesical  tuberculosis  is  found  more  frequently  in  males 
than  in  females,  and  is  a  disease  of  early  and  middle  life 
(seventeen  and  forty  years  of  age).  In  the  male  the  disease 
is  frequently  associated  with  tuberculosis  of  the  seminal  vesi- 
cles and  of  the  prostate.  The  resistance  of  the  mucous 
membrane  of  the  bladder  to  tubercle  bacilli  is  quite  marked  ; 
in  some  cases  of  tuberculosis  of  the  kidney  the  bladder  may 
be  irrigated  with  urine  containing  tubercle  bacilli  for  years 
without  becoming  tubercular. 

Prominent  Symptoms. — The  symptoms  of  vesical  tuber- 
culosis are  similar  to  those  of  stone  in  the  bladder.  The 
disease  is  initiated  by  a  frequent  desire  to  urinate,  by  pain 
after  emptying  the  bladder,  with  slight  hematuria  at  longer 
or  shorter  intervals.  Later  in  the  disease  intermittent 
hemorrhage  becomes  a  conspicuous  clinical  symptom,  but 
it  is  never  so  profuse  as  in  tumor  of  the  bladder.  Reten- 
tion and  incontinence  of  urine  are  quite  common. 

Character  of  the  Urine.— Quantity.— The  twenty-four- 
hour  quantity  is  usually  diminished,  although  it  may  be 
slightly  increased. 

Color. — Pale  ;  sometimes  bloody.  The  urine  is  gener- 
ally quite  turbid  from  the  pus,  blood,  etc.,  in  suspension. 

Reaction. — Nearly  always  acid,  except  when  the  urine 
contains  a  large  amount  of  blood,  when  it  may  be  neutral 
or  alkaline. 
-    Specific  Gravity. — Usually,  below  the  normal —  i  o  i o  to 

1015. 

Normal  Solids. — Relatively  and  absolutely,  diminished. 

Albumin. — The  quantity  will  depend  chiefly  on  the 
amount  of  blood  and  pus  present ;  it  usually  varies  between 
a  slight  trace  and  a  large  trace.  In  case  of  abundant  hema- 
turia the  quantity  of  albumin  will,  of  course,  be  high — }i 
to  3<(  of  I  per  cent. 

Sediment. — Abundant.  Chiefly  pus,  which  is  generally 
free,  but  may  be  slightly  clumped.  Considerable  squamous 
epithelium  and  many  small  round  cells,  some  of  which  are 
fatty  ;  a  few  (sometimes  numerous)  blood  globules.  The 
sediment  also  contains  tubercle  bacilli. 

As  in  tuberculosis  of  other  parts  of  the  urinary  tract. 


348  DISEASES  OF  THE  URINARY  TRACT. 

the  symptoms  are  variable  and  often  misleading.  Even  the 
presence  of  tubercle  bacilli  in  the  urine,  indicating  as  it 
does  tuberculosis  of  the  urinary  system,  does  not  locate  the 
anatomic  seat  of  the  disease.  The  presence  of  tubercle 
bacilli  and  squamous  epithelium,  which  are  more  or  less  inti- 
mately mixed  with  the  pus,  makes  the  diagnosis  of  vesical 
tuberculosis  probable. 

The  prognosis  in  this  condition  is  usually  grave.  Spon- 
taneous recovery  is  exceedingly  rare.  If  the  disease  be 
mild  and  limited  to  the  bladder,  it  may  remain  in  a  latent 
condition  for  years.  There  is  always  danger  of  an  exten- 
sion of  the  tubercular  process  to  the  kidney,  which  is  soon 
followed  by  a  suppurative  pyelonephritis.  There  can  be 
but  little  doubt  that  appropriate  general  and  local  treat- 
ment will  prolong  life  and  alleviate  the  distressing  symp- 
toms. 

In  all  cases  of  cystitis  in  which  the  cause  of  the  disease 
is  not  obvious  the  urinary  sediment  should  be  very  care- 
fully searched  for  tubercle  bacilli.  In  case  the  organisms 
can  not  be  found  a  guinea-pig  should  be  inoculated  with  a 
portion  of  the  sediment  (^  to  i  c.c),  and  the  result  of  this 
experiment  obtained,  before  eliminating  the  diagnosis  of 
tuberculosis.  (See  Detection  of  Tubercle  Bacilli  in  the 
Urinary  Sediment,  p.  323.) 


TUMORS  OF  THE  BLADDER. 

Tumors  of  the  bladder  may  be  either  benign  or  malig- 
nant. 

The  benign  tumors  include  the  fibromata,  fibromyx- 
omata,  and  papillomata  ;  of  these  the  latter  are  by  far  the 
most  frequent.  Fibromata  and  fibromyxoviata  grow  from 
the  submucous  coat  of  the  bladder ;  they  are  either  sessile 
or  pedunculated,  and  are  covered  by  unaltered  mucous 
membrane  or  by  villi.  Papillomata  grow  from  the  super- 
ficial layer  of  the  mucous  membrane ;  they  appear  as  red 
vascular  masses,  usually  with  long  pedicles,  and  occasion- 
ally they  are  sessile.  Sometimes  the  papillae  are  long  and 
slender  and  float  in  the  urine  in  numerous  filaments  from  a 
common  base  ;  sometimes  the  mass  has  a  cauliflower  ap- 
pearance, this  form  of  tumor  constitutes  the  so-called  villous 
growtJi  of  the  bladder.  (In  Fig.  53  the  masses  represent 
small  portions  of  very  small  villi   in   which   characteristic 


TUMORS  OF  THE  BLADDER. 


349 


small  caudate  cells  are  arranged  about  a  central  cone  of 
fibrous  tissue,  blood-vessels,  etc.  The  caudate  cells  have 
prominent  and  relatively  large  nuclei,  and  are  somewhat 
larger  than  the  average  cell  from  the  superficial  layer  of  the 
pelvis  of  the  kidney.  In  papillomatous  disease  of  the 
bladder  cells  of  this  kind  may  be  found  in  the  sediment 
singly  or  in  clumps.)    Frequently,  they  undergo  ulceration  ; 


^»fe 

fe^i^ 

?-          % 

W&f/ . 

^ 

« 

cv         < 

b 

"V  ' 

Fig-  53- — Portions  of  a  villous  growth  of  the  bladder:  a.  Magnified  190  diameters; 
d,  magnified  370  diameters. 


they  sometimes  bleed  very  freely.  Nearly  all  vesical 
growths  tend  to  assume  a  papillomatous  character.  When 
the  fibrous  elements  are  numerous,  the  structure  is  denser  ; 
this  constitutes  the  fihropapillonia.  There  is  reason  to  be- 
lieve that  a  growth  originally  purely  papillomatous  may 
become  malignant  in  its  later  stages  ("  American  Text- 
book of  Surgery  "). 


350  DISEASES  OF  THE   URINARY  TRACT. 

Malignant  tumors  of  the  bladder,  although  for  the  most 
part  papillomatous,  belong  either  to  the  order  of  sarcomata 
or  to  carcinomata.     (See  Cancer  of  the  Prostate.) 

The  prominent  symptoms  of  tumor  of  the  bladder  are 
those  of  a  chronic  cystitis.  (See  p.  345.)  Intermittent 
hematuria  is  a  common  symptom.  Pain  is  usually  not  so 
marked  as  in  the  average  case  of  chronic  cystitis,  and  it 
may  even  be  absent,  especially  if  the  disease  does  not  in- 
vade the  trigone  (Fenwick).  Frequency  of  micturition  is 
an  early  and  constant  symptom. 

Character  of  the  Urine. — The  urine  has  much  the  same 
characteristics  as  in  chronic  cystitis,  except  that  the  reaction 
is  generally  acid  ;  there  is  a  bloody  or  smoky  color,  and  on 
account  of  the  quantity  of  blood,  a  comparatively  high 
percentage  of  albumin.  Blood  may  be  present  in  large 
amount ;  in  fact,  the  quantity  of  blood  is  often  greater  than 
in  almost  any  other  disease  of  the  urinary  tract.  Large 
blood-clots  may  partially  fill  the  bladder,  and  not  infre- 
quently they  are  the  cause  of  retention  of  urine.  The 
blood  is  usually  not  so  intimately  mixed  with  the  urine  as 
when  it  comes  from  the  kidney. 

After  the  urine  has  settled  and  the  blood  has  been  de- 
stroyed (see  p.  231),  shreds  are  frequently  seen  floating  in 
the  urine.  Upon  microscopic  examination  these  may  be 
found  to  consist  of  pus  and  cells  embedded  in  mucin,  or 
bits  of  tissue  perhaps  resembling  the  mass  represented  in 
figurc  53  (villous  growth).  Inferences  as  to  the  nature 
of  these  shreds — whether  malignant  or  benign — can  not 
usually  be  drawn  from  a  microscopic  examination  of  the 
sediment.  Sometimes,  as  previously  stated,  the  sediment 
contains  caudate  cells,  single  or  in  clumps,  which  will  lead 
to  the  diagnosis  of  villous  growths.  Likewise,  medium  and 
small  round  and  irregular  cells  with  prominent  and  rela- 
tively large  nuclei  may  be  found,  suggesting  a  new  growth 
of  the  bladder.  Usually,  the  epithelial  elements  are  a  pre- 
dominant feature  of  the  sediment. 

Following  the  introduction  of  sounds  or  bougies  into  the 
bladder,  the  urine  often  contains  cells  (caudate,  large  and 
small  round)  that  have  been  mechanically  detached  from 
the  mucous  surface.  These  cells  are  found  both  singly  and 
in  clumps  ;  and  care  should  be  taken  not  to  mistake  them 
for  cells  of  a  new  growth. 


ACUTE  PROSTATITIS.  351 

PROSTATITIS. 

An  inflammation  of  the  prostate  gland  may  be  either 
acute  or  chronic,  and  parenchymatous  or  foHicular. 

In  the  parciicliymatous  form  the  inflammation  afiects  the 
whole  substance  of  the  gland,  and  constitutes  the  severer 
acute  forms  of  prostatitis. 

ACUTE  PROSTATITIS  (PARENCHYMATOUS). 

Causes. — Among  the  causes  of  this  condition  may  be 
enumerated  gonorrhea,  urethral  stricture,  extreme  and  pro- 
longed sexual  excitement,  concentrated  and  highly  acid 
urine,  exposure  to  cold  and  wet,  violence  from  instruments, 
fragments  of  calculi,  trauma,  etc.  It  may  also  result  from 
the  action  of  chemic  irritants,  strong  urethral  injections,  the 
internal  administration  of  cantharides,  etc.  Gonorrheal  in- 
flammation, after  the  first  week,  may  extend  to  the  prostate, 
particularly  if  the  patient  indulges  in  liquor,  sexual  inter- 
course, or  uses  strong  injections  throwing  them  deep  into 
the  urethral  canal,  or  takes  violent  exercise.  Sometimes, 
during  gonorrhea,  the  prostate  becomes  inflamed  without 
an  exciting  cause.  The  inflammation  behind  a  stricture 
may  extend  back  and  involve  the  prostate  in  the  same  way. 
Sexual  hyperemia,  too  much  prolonged  or  too  often  re- 
peated, may  lead  to  an  acute  prostatitis. 

Prominent  Symptoms. — The  organ  swells  rapidly,  put- 
ting the  capsule  on  the  stretch,  and  often  reaches  the  size  of  a 
small  orange.  The  exploring  finger  in  the  rectum  strikes  at 
once  against  an  unevenly  enlarged  mass  that  projects  into 
the  cavity  of  the  intestine.  It  is  very  tense  and  hot,  ex- 
tremely tender,  and  can  be  felt  distinctly  to  pulsate.  The 
lightest  touch,  even  the  presence  alone  of  the  finger  in  the 
rectum,  at  once  excites  a  marked  desire  to  micturate  ;  pres- 
sure over  the  pubes  has  the  same  result.  The  patient  may 
have  an  unnatural  desire  to  defecate  ;  if  he  endeavors  to 
do  this,  he  strains  ineffectively,  causing  pain,  but  getting  no 
relief.  There  is  subjectively  a  feeling  of  weight,  heat,  and 
throbbing,  and  sometimes  pain  in  the  back  and  limbs.  The 
stream  of  urine  is  usually  small,  and  occasionally  there  is 
complete  retention  of  urine  as  a  result  of  the  swelling. 
Almost  invariably  there  are  an  associated  congestion  of  the 
vesical  neck  and  a  consequent  extreme  tenesmus.  The  urine 
causes  pain  in  its  passage,  but  the  pain  is  most  severe  when 


352  DISEASES  OF  THE  URINARY  TRACT. 

the  last  drops  of  urine  are  being  expelled.  There  is  gener- 
ally febrile  disturbance,  and  the  patient  is  usually  irritable, 
despondent,  and  suspicious. 

Character  of  the  Urine. — Quantity. — The  twenty-four- 
hour  quantity  is  small — generally  between  500  and  lOOO  c.c. 

Color. — High  or  bloody. 

Reaction. — Strongly  acid. 

Specific  Gravity. — Usually  high — 1025  to  1035. 

Normal  Solids.  —  Relatively,  increased;  absolutely, 
diminished.  If  the  acute  process  lasts  more  than  two  or 
three  days,  the  solids  will  be  much  diminished  absolutely. 

Albumin. — Usually  between  yi  and  3^  of  i  per  cent.  ; 
but  the  quantity  is  dependent  chiefly  on  the  amount  of 
blood  and  pus  present. 

Sediment. — Chiefly  normal  blood.  Considerable  pus, 
both  free  and  in  clumps  ;  many  small  round  cells  and  a 
marked  excess  of  cells  from  the  prostatic  region  (neck  of 
bladder)  ;  frequently  there  are  spermatozoa  and  cells  from 
the  seminal  passages.  Occasionally,  casts  of  the  prostatic 
ducts  are  present,  and  with  difficulty  distinguished  from 
casts  of  the  renal  tubules,  which  may  also  be  present  as  a 
result  of  a  coincident  renal  congestion. 

Diagnosis. — The  clinical  picture  of  the  case  is  generally 
sufficient  for  a  diagnosis  without  an  analysis  of  the  urine. 
In  some  instances,  however,  the  diagnosis  between  an  acute 
prostatitis  and  acute  cystitis  is  not  easy,  but  can  often  be 
made  by  attention  to  the  following  points  : 

Acute  Prostatitis.  Acute  Cystitis. 

Perineal  and  rectal  pain.  Possibly  a  little    tenderness    of    the 

perineum  on  pressure,  but  little  or 
no  rectal  pain. 
Pain   violent   and    throbbing,   aggra-       Pain  burning,  not  especially  affected 

vated  during  defecation.  by  defecation. 

Stream  of  urine  diminished  in  size.  Size  of  stream  not  usually  affected. 

Retention  of  urine  common.  Retention  of  urine  much   less   com- 

mon. 
Rectal    examination    shows   enlarge-       No  prostatic  enlargement  or  tender- 
ment  and  extreme  tenderness  of  the  ness  recognizable  on  rectal  exam- 

prostate,  ination. 

Urinary  sediment  contains  blood,  pus.        Urinary    sediment    contains,    besides 
marked  excess  of  epithelium  from  blood    and   pus,    much    squamous 

prostatic  region,   spermatozoa,  and  epithelium,  usually  no  marked  ex- 

prostatic  casts.  cess  of  cells  from  prostatic  region, 

and   no  spermatozoa  nor    prostatic 
casts. 

A  greater  or  less  involvement  of  the  neck  of  the  bladder 
is  often  an  accompaniment  of  an  acute  prostatitis. 


PROSTATIC  ABSCESS.  353 

PROSTATIC  ABSCESS. 

An  abscess  of  the  prostate  is  liable  to  form  as  the  result 
of  a  parenchymatous  inflammation  of  the  organ.  There  may 
be  one  or  more  purulent  foci,  or  the  whole  substance  of  the 
prostate  contained  within  its  fibrous  capsule  may  suppurate. 

The  symptoms  are  in  many  respects  similar  to  those  of 
an  acute  prostatitis.  A  sharp  chill  or  a  series  of  rigors 
announces  the  beginning  of  suppuration.  As  the  pus 
forms  it  presses  upon  the  already  narrowed  canal  of  the 
urethra  ;  and,  finally,  unless  the  abscess  is  veiy  small, 
obliterates  it  entirely,  causing  retention  of  urine.  There 
are  usually  local  throbbing  and  lancinating  pain.  These 
abscesses,  left  alone,  discharge  into  the  bladder,  urethra, 
rectum,  or  through  the  perineum.  When  such  an  abscess 
opens  spontaneously,  all  pain  and  discomfort  are  immedi- 
ately relieved.  A  small  purulent  collection  in  the  prostate 
may  empty  itself  gradually  into  the  urethra  by  one  or 
more  minute  openings  ;  in  such  cases  the  diagnosis  of  a 
prostatic  abscess  is  not  easily  made. 

Character  of  the  Urine. — This  will  vary  according  to 
circumstances  :  If  the  abscess  is  forming  and  has  not  yet 
opened,  the  urine  will  be  concentrated,  of  high  color,  and 
high  specific  gravity,  containing  a  very  small  amount  of 
albumin  ;  the  sediment  will  consist  of  a  few  leucocytes, 
blood  globules,  and  an  excess  of  cells  from  the  neck  of  the 
bladder  or  prostatic  urethra — in  other  words,  di  fever  tirine, 
in  which  the  sediment  presents  the  evidences  of  an  irrita- 
tion in  the  prostatic  region.  On  the  other  hand,  if  the 
abscess  has  ruptured,  the  urine,  with  the  exception  of 
the  sediment,  will  present  the  characteristics  of  that  of 
severe  chronic  prostatitis.  The  sedhncnt,  which  is  abundant 
and  often  greenish  in  color,  will  consist  chiefly  of  pus,  both 
free  and  in  clumps,  that  in  clumps  usually  being  much 
degenerated ;  many  small  round  cells,  some  fatty,  and 
generally  a  few  compound  granule  cells  ;  and  few  or  num- 
erous blood  globules.  There  is  also  an  excess  of  cells 
from  the  prostatic  region. 

CHRONIC  PROSTATITIS. 

Causes. — A  chronic  inflammation  of  the  prostate  gland 
may  be  the  result  of  an    acute   prostatitis.      In    some    in- 
stances, as  following  sexual  excesses,  masturbation,  etc.,  the 
23 


354  DISEASES  OF  THE  URINARY  TRACT. 

pathologic  process  in  the  organ  starts  as  a  sHght  irritation 
that  gradually  increases,  finally  becoming  a  well-marked 
chronic  condition  without  passing  through  an  acute  stage. 
A  chronic  prostatitis  may  result  from  stricture  of  the  urethra, 
contracted  meatus,  phimosis,  hypertrophy  of  the  prostate  in 
persons  past  the  age  of  fifty-five,  tuberculosis,  trauma,  irri- 
tation by  crystalline  elements,  etc. 

Prominent  Symptoms. — Perhaps  the  most  prominent 
symptom  of  this  condition  is  frequency  of  micturition. 
There  are  usually  some  pain  and  a  feeling  of  uneasiness  at 
the  neck  of  the  bladder,  especially  toward  the  close  of  uri- 
nation, and  often  pain  at  the  end  of  the  penis  and  along 
the  under  surface  of  the  urethra.  There  may  be  a  muco- 
purulent discharge  from  the  urethra,  but  this  is  not  gen- 
erally the  case.  Defecation  is  sometimes  painful.  Walk- 
ing causes  pain,  and  crossing  the  legs  decidedly  increases 
it.  As  the  disease  advances,  the  sitting  posture  be- 
comes painful.  Retention  of  urine  is  common.  Constitu- 
tional disturbance  may  be  absent,  particularly  in  mild 
cases  ;  when  the  disease  is  marked,  however,  there  may  be 
more  or  less  fever  and  mental  depression.  The  finger  in 
the  rectum  may  find  slight  enlargement  and  at  times  detect 
extra  sensibility. 

If  the  disease  is  the  result  of  Jiypertrophied  prostate,  not 
only  will  the  enlargement  be  apparent  to  the  finger  in  the 
rectum,  but  signs  of  mechanical  obstruction  to  the  outflow 
of  urine  will  be  prominent  ;  the  stream  will  be  interrupted 
and  show  a  lack  of  force  ;  the  patient  will  be  unable  to 
completely  empty  the  bladder,  only  passing  that  which  is 
in  excess.  This  "residual"  urine  may  remain  stationary 
in  amount,  but  more  often  it  gradually  increases  until,  in 
some  cases  in  which  both  hypertrophy  of  the  prostate  and 
atony  of  the  bladder  are  marked,  only  an  ounce  or  two  of 
urine  can  be  evacuated  voluntarily,  although  catheterization 
will  show  that  the  bladder  contains  possibly  a  pint  or  more. 
The  decomposition  of  the  retained  urine  invariably  results 
in  a  chronic  cystitis  ;  often  a  pyelonephritis  develops ; 
general  sepsis  occurs  ;  and  the  patient  becoming  uremic 
dies  during  coma. 

Fortunately,  a  fatal  termination  is  not  the  outcome  of  all 
cases  of  chronic  prostatitis  ;  some  are  amenable  to  treatment 
and  entirely  recover,  especially  the  milder  cases  and  those 


CHRONIC  PROSTATITIS.  355 

which  are  not  tubercular,  or  those  in  which  an  abscess  of  the 
prostate  lias  not  developed. 

Character  of  the  Urine. — Quantity. — The  total  quantity 
for  twenty-four  hours  is  usually  between  800  c.c.  and 
1200  c.c. 

Color. — Pale.  The  urine  is  generally  turbid,  due  to  the 
presence  of  a  large  amount  of  pus  in  suspension. 

Reaction. — Usually  acid  ;  if  there  is  an  accompanying 
chronic  cystitis,  the  reaction  may  be  alkaline,  especially  in 
cases  of  hypertrophy  of  the  prostate. 

Specific  Gravity. — This  will  generally  be  found  to  vary 
between  1012  and    1018 — average  about  10 15. 

Normal  Solids. — Both  relatively  and  absolutely,  dimin- 
ished ;  the  degree  of  diminution  will  depend  largely  on  the 
amount  of  constitutional  disturbance. 

Albumin. — The  quantity  of  albumin  will  depend  on  the 
amount  of  pus  and  blood  ;  it  usually  varies  between  a  very 
slight  trace  and  ^  of  i  per  cent.  In  case  there  is  an  accom- 
panying disturbance  or  disease  of  the  kidney  the  amount  of 
albumin  will  be  proportionately  higher. 

Sediment. — This  is  abundant,  and  consists  chiefly  of  pus, 
both  free  and  in  clumps  ;  many  small  round  cells,  some  of 
which  are  fatty  ;  also  an  excess  of  cells  from  the  neck  of  the 
bladder  and  prostatic  urethra  ;  a  few  (sometimes  numerous) 
blood  globules  ;  and  sometimes  spermatozoa,  and  the  highly 
granular  cells  from  the  seminal  passages.  Prostatic  plugs 
(cylinders  of  long  diameter  resembling  large  renal  casts  or 
bodies  of  irregular  shapes  from  dilated  ducts  or  cavities), 
sometimes  with  spermatozoa  embedded,  are  of  frequent 
occurrence,  especially  in  the  mild  (follicular)  forms  of 
chronic  prostatitis.  Frequently,  the  sediment  contains  large 
and  small  shreds  that  will  be  found  to  consist  of  pus,  small 
round  cells,  and  dense  cells  from  the  prostatic  region,  which 
are  embedded  in  mucin  (nucleo-albumin).  If  there  is  an 
accompanying  chronic  cystitis,  as  is  the  rule  in  cases  of 
hypertrophied  prostate,  the  sediment  will  contain  more  or 
less  squamous  epithelium,  and  frequently  crj^stals  of  triple 
phosphate.  A  renal  disturbance  that  is  probably  indirectly 
due  to  the  chronic  prostatitis,  and  perhaps  the  result  of  the 
absorption  of  toxines,  is  not  uncommon.  An  occasional  or 
a  few  renal  casts  may  be  found  in  the  sediment,  which  are 
sometimes  distinguished  with  difficulty  on  account  of  the 
abundance  of  pus. 


356  DISEASES  OF  THE  URINARY  TRACT. 


TUBERCULAR  PROSTATITIS. 

This  disease  of  the  prostate  is  almost  invariably  associ- 
ated with  tuberculosis  of  some  other  part  of  the  genito- 
urinary tract.  The  disease  occurs  in  tubercular,  debilitated 
subjects,  its  chief  feature  being  cheesy  degeneration,  situ- 
ated for  the  most  part  in  the  ducts  and  follicles  of  the 
organ.  True  miliary  tubercle  does  not  seem  to  occur  in 
the  prostate. 

The  symptoms  are  those  of  a  severe  chronic  prostatitis. 
Generally,  there  is  more  or  less  frequency  of  micturition. 
The  symptoms  become  spontaneously  better  or  worse,  but 
the  general  tendency  is  toward  steady  aggravation.  The 
cheesy  masses  ulcerate,  form  abscesses  that  break  in  all 
directions,  leaving  open  cavities  or  fistulas.  Intermittent 
hemorrhage  from  the  urethra  is  quite  a  constant  symptom. 
The  disease  is  probably  more  common  than  has  hitherto 
been  supposed. 

Character  of  the  Urine. — Quantity. — The  twenty-four- 
hour  quantity  is  usually  not  far  from  looo  c.c. 

Color. — Pale.  The  freshly  passed  urine  is  usually  tur- 
bid, and  sometimes  it  is  opaque. 

Reaction. — Acid. 

Specific  Gravity. — Usually,  below  the  average  normal, 
varying  between  1012  and  1018. 

Normal  Solids. — Both  relatively  and  absolutely,  dimin- 
ished, but  dependent  largely  on  the  extent  of  the  constitu- 
tional disturbance  and  the  appetite. 

Albumin. — This  varies  as  the  amount  of  pus  and  blood 
present  in  the  urine  ;  it  is  usually  from  a  slight  trace  to  a 
large  trace. 

Sediment. — This  is  generally  abundant  and  consists 
chiefly  of  pus  both  free  and  in  clumps  ;  a  large  number 
of  small  round  cells,  some  of  which  are  fatty  ;  often  an 
excess  of  dense  round  cells  from  the  neck  of  the  bladder 
and  prostatic  urethra ;  and  a  few  (sometimes  numerous) 
blood  globules.  When  the  freshly  passed  urine  is  examined, 
the  pus  is  often  found  to  be  ameboid.  Large  clumps  of 
degenerated  and  disintegrated  pus  and  cells  are  occasion- 
ally found. 

A  urine  having  the  above  characteristics  should  always 
be  examined  for  tubercle  bacilli,  which,  however,  are  usu- 
ally difficult   to  find,  but   occasionally  they  are  present  in 


CANCER  OF  THE  PROSTATE.  357 

large  numbers.  (For  details  concerning  the  examination 
for  tubercle  bacilli,  see  p.  323.)  If  the  bacilli  are  not  found 
in  the  sediment  after  repeated  trials,  a  guinea-pig  should  be 
inoculated  with  a  portion  of  the  sediment  in  order  to  deter- 
mine positively  their  presence  or  absence. 

CANCER  OF  THE  PROSTATE. 

Primary  cancer  of  the  prostate  is  exceedingly  rare.  It  is 
usually  secondary  to  carcinoma  or  sarcoma  elsewhere,  es- 
pecially in  the  kidney  or  testicle.  The  scirrhous,  melanotic, 
and  medullary  forms  have  all  been  noted  ;  of  these  the  latter 
is  perhaps  the  most  frequent. 

The  symptoms  at  first  are  those  caused  by  an  in- 
crease in  the  size  of  the  organ,  such  as  obstruction  to 
the  outflow  of  urine,  frequency  of  micturition,  and  pain. 
The  early  symptoms  are  not  pathognomonic.  Later  in 
the  disease  the  cancerous  cachexia,  glandular  enlargement, 
and  the  evidences  of  a  cancerous  affection  elsewhere  in  the 
body  are  usually  sufficiently  prominent  to  suggest  cancer 
of  the  prostate.  Rectal  examination  may  be  of  value  in 
determining  the  form  of  cancer  that  exists.  Hematuria  is 
common. 

Urine. — An  analysis  of  the  urine  is  often  of  but  little 
value  in  the  diagnosis  of  cancer  of  the  prostate.  The  charac- 
teristics of  the  urine  are  usually  those  of  chronic  prostatitis. 
The  urine  may,  from  time  to  time,  contain  a  large  amount  of 
blood.  Occasionally,  the  presence  of  a  large  number  of 
medium  and  small  round  cells,  with  relatively  large  and 
prominent  nuclei,  may  suggest  the  presence  of  malignant 
disease  of  the  prostate. 

The  diagnosis  of  cancer  of  the  prostate  is  very  difficult 
if  the  disease  appears  after  the  organ  has  from  any  cause 
become  hypertrophied. 

URETHRITIS. 

Of  all  the  diseases  encountered  in  genito-urinary  surgery 
urethral  inflammation  is  the  most  common.  Although 
strictly  a  local  affection,  and  exerting  little  or  no  poisonous 
action  upon  the  blood,  it  is  the  most  venereal  of  all  venereal 
diseases,  since  it  is  the  commonest  malady  acquired  during 
the  copulative  act. 


358  DISEASES  OF  THE  URINARY  TRACT. 

The  term  nrctJiritis  signifies  simple  inflammation  of  the 
urethra.  The  term  gonorrJiea,  although  etymologically 
inaccurate,  indicating  as  it  does  a  flow  of  semen,  has  been, 
and  is  still,  universally  employed  and  considered,  especially 
among  the  laity,  to  have  the  same  meaning  as  the  term 
urethritis.  But  a  gonorrhea  is  in  all  probability  due  to  a 
specific  organism — the  gonococcus.  A  gonorrhea  is  a  ure- 
thritis, but  the  converse  is  by  no  means  always  true,  since 
urethral  inflammation  may  have  a  variety  of  causes  other 
than  an  infection  with  the  gonococcus.  For  practical  pur- 
poses it  is  better  to  retain  the  two  terms,  calling  that  gonor- 
rhea that  has  been  unmistakably  derived  from  an  individual 
of  the  other  sex  with  a  gonorrhea,  and  reserving  the  term 
urethritis  for  all  inflammatory  urethral  discharges  having 
another  origin.  Or  the  term  simple  jwcthritis  may  be  used 
to  indicate  those  conditions  in  which  the  gonococcus  is 
absent,  and  specific  Jiretlwitis  to  indicate  those  in  which  the 
gonococcus  is  present. 

Causes. — Simple  Urethritis. — Authentic  cases  are  on 
record  of  well-marked  urethritis  following  exposure  to 
leucorrheal  discharges  ;  to  the  pus  from  a  healthy  abscess, 
or  from  a  purulent  bronchial  catarrh  ;  to  the  secretion  from 
an  endocervicitis  or  endometritis  ;  to  the  discharge  result- 
ing from  ulceration  or  malignant  disease  of  the  uterus  ;  to 
menstrual  fluid  or  acrid  vaginal  discharges ;  to  power- 
ful injections  ;  to  the  irritating  influences  of  crystalline  ele- 
ments or  the  passage  of  a  calculus  ;  to  catheterization  ;  to 
exposure  to  cold  and  wet ;  to  a  concentrated  urine  ;  to 
the  action  of  certain  drugs — cantharides  ;  to  the  extension 
of  inflammatory  diseases  from  the  prostate  or  bladder  ; 
occasionally,  to  the  free  use  of  alcoholic  drinks,  especially 
beer — the  so-called  "  beer  clap  "  ;  and  to  many  other  non- 
specific causes. 

Specific  Urethritis  or  Gonorrhea.  ^ — There  is  scarcely 
a  shadow  of  doubt  but  that  the  cause  of  gonorrhea  is  the 
gonococc7is  of  Neisser.  (See  p.  266.)  The  microscopic 
detection  of  this  micro-organism  is,  so  far  as  known,  the 
only  safe  means  of  distinguishing  between  specific  urethritis 
and  a  simple  urethritis. 

Prominent  Symptoms. — The  most  constant  symptom  of 
a  simple  urethritis  is  a  urethral  discharge.     On  the  first, 

1  For  details  concerning  thi.s  disease,  see  special  works  on  genito-urinary 
surgery. 


URETHRITIS.  359 

second,  or  third  day  after  having  indulged  in  sexual  inter- 
course, perhaps  with  a  partner  having  an  extensive  leucor- 
rhea,  the  first  symptom  noticed  is  a  slight,  uneasy  sensation 
at  the  meatus,  a  Httle  smarting,  and  a  pearly  drop  of  pus  at 
the  meatus  ;  or  perhaps  the  lips  of  the  urethra  are  glued 
together  in  the  morning  on  rising.  The  inflammation  will 
probably  not  run  high  or  last  long,  and  upon  microscopic 
examination  specific  gonococci  will  not  be  found.  In  some 
instances  the  discharge  is  -profuse,  the  inflammation  runs 
high  and  continues  for  weeks,  and  with  the  exception  of 
the  absence  of  gonococci  the  disease  can  not  be  distinguished 
from  true  gonorrhea.  There  may  be  pain  all  along  the 
pendulous  urethra,  and  the  canal  is  sensitive  to  pressure  ; 
the  meatus  feels  hot  and  sore,  and  urination  is  frequent  and 
painful.  Chordee  may  be  as  prominent  as  in  a  true  gonor- 
rheal inflammation.  An  acute  prostatitis  or  cystitis  may 
follow.  General  systemic  disturbance  is  sometimes  marked. 
Organic  stricture  may  follow  a  simple  urethritis. 

Character  of  the  Urine. — Quantity. — Usually  dimin- 
ished— 800  c.c.  to  1200  c.c. 

Color. — Normal  or  high.  The  urine  is  generally  more 
or  less  turbid  owing  to  the  pus  and  epithelial  cells  in  sus- 
pension. 

Specific  Gravity. — From  1020  to  1030,  but  dependent 
on  the  concentration  of  the  urine. 

Reaction. — Usually,  strongly  acid. 

Normal  Solids. — Relatively,  normal  or  increased  ;  abso- 
lutely, normal.  In  those  cases  in  which  marked  constitu- 
tional disturbance  exists  the  solids  are  generally  absolutely 
diminished. 

Albumin. — Albumin  is  invariably  present  ;  the  quantity 
is  dependent  on  the  amount  of  blood  and  pus  present  ;  it 
usually  varies  between  iht  slightest  possible  trace  and  a  large 
trace. 

Sediment. — Chiefly  dense  pus  ;  many  urethral  cells 
and  an  occasional  (or  few  or  numerous)  blood  globule  ; 
often  an  excess  of  mucin  (nucleo-albumin).  If  the  inflam- 
matory process  is  most  marked  in  the  prostatic  urethra, 
cells  from  that  region,  as  well  as  cells  from  the  neck  of  the 
bladder,  will  be  found  with  the  pus.  In  case  of  an  organic 
stricture,  or  gleet,  the  pus  and  cells  will  be  found  chiefly  in 
shreds  of  mucin  (nucleo-albumin). 

The  urine  should  be  carefully  watched  for  evidences  of 


360  DISEASES  OF  THE  URINARY  TRACT. 

a  complicating  prostatitis  or  cystitis,  in  which  case  the 
amount  of  pus  will  be  larger,  and  the  quantity  of  blood 
greater  than  in  a  urethritis.  There  will  also  be  an  unusual 
number  of  cells  from  the  prostatic  region,  and,  perhaps, 
casts  of  the  prostatic  ducts  and  spermatozoa  ;  or,  in  case  of 
cystitis,  an  abundance  of  squamous  epithelium. 

In  all  cases  of  urethritis  of  doubtful  origin,  a  thorough 
search  for  gonococci  should  be  made.  (For  method  of 
staining,  see  p.  266.) 

CHYLURIA. 

This  is  a  condition  that  results  from  a  pathologic  commu- 
nication   between   the  lymphatic   system   and   the    urinary 


o  <^>!?<^<^^«         *Q^er  ^"P^ 


C^°^-^M 


,'^*v 


Fig.  54. — The  filaria  sanguinis  hominis.  The  head  can  be  seen  at  the  left  of  cut : 
the  tail,  at  the  right.  The  parasite  is  inclosed  within  a  hyaline  capsule.  Magnified 
2S0  diameters. 

passages.  Under  such  circumstances  the  urine  has  a  milky 
appearance,  due  to  the  presence  of  chyle.  The  cause  of 
this  disease  is  a  parasite — the  filaria  sangtihds  Jiominis  (see 
Fig.  54) — that  invades  the  blood  and  obstructs  the  lymph- 
atic channels,  finally  resulting  in  the  rupture  of  a  lymph- 
atic vessel.  The  disease  appears  to  be  confined  chiefly  to 
the  tropics  (India,  China,  Bermuda,  Brazil,  Australia,  and  the 
West  Indies),  or  to  those  individuals  who  have  spent  much 
of  their  lives  there.  Guiteras  has  shown  that  the  disease  is 
not  uncommon  in  the  Southern  States.  It  is  of  very  rare 
occurrence  in  the  New  England  States,  the  author  having 
met  with  only  one  case  ;  in  this  case  the  filaria  was  readily 


CHYLURIA.  361 

found  in  the  blood.  Besides  the  endemic  form  of  this  dis- 
ease, it  is  very  rarely  met  with  following  traumatism  and 
disease  in  which  an  abnormal  communication  has  formed 
between  the  lymphatics  and  the  urinary  tract.  Osier  refers 
to  a  nonparasitic  form  of  chyluria.  The  disease  affects  alike 
both  males  and  females,  and  may  occur  at  any  age. 

A  peculiar  feature  of  the  parasite  is  that  it  works  at 
night,  or  while  the  patient  is  in  the  recumbent  position,  being 
quiescent  while  the  patient  is  up  and  about.  In  conse- 
quence, the  night  urine  is  milky,  while  that  passed  during 
the  day  is  clear  and  usually  of  normal  color  ;  but  if  the  in- 
dividual sleeps  or  reclines  during  the  day,  the  urine  passed 
at  that  time  is  milky. 

Characteristics  of  the  Urine.— The  characteristics  of  a 
chylous  urine  are  as  follows  : 

Quantity. — This  is  usually  below  the  average  normal — 
1500  c.c;  it  may,  however,  be  normal  or  slightly  increased. 

Color. — Milky.  Opaque.  Occasionally,  the  urine  is 
slightly  tinged  with  blood. 

Reaction. — Acid. 

Specific  Gravity. — Usually,  normal  or  sHghtly  dimin- 
ished ;  it  may  be  as  low  as  10 10,  particularly  if  the  quantity 
of  urine  is  moderately  increased. 

Normal  Solids. — Relatively,  normal  or  slightly  dimin- 
ished. Absolutely,  slightly  diminished,  especially  the  urea 
and  chlorides.  The  phosphates  may  be  moderately  in- 
creased. 

Albumin. — This  will  depend  chiefly  on  the  amount  of 
blood  present  in  the  urine.  Usually,  the  quantity  varies  be- 
tween the  slightest  possible  trace  and  a  trace.  Owing  to  the 
opacity  of  the  urine,  the  usual  tests  for  albumin  can  not  be 
satisfactorily  applied.  It  is  necessary  to  first  remove  the  fat 
in  suspension  by  shaking  with  ether ;  then  either  the  nitric 
acid  or  the  heat  test  can  be  applied  to  the  clear  urine  in  the 
usual  manner. 

Sediment. — Slight ;  often  no  sediment  is  visible  on  in- 
spection. Chiefly  fine  granular  matter,  a  few  leucocytes, 
and  an  occasional  (or  few,  and  sometimes  numerous)  blood 
globule.  Perhaps,  rarely  a  hyaHne  and  granular  cast  and 
renal  cell  may  be  found.  Casts  are  not  always  present.  No 
fat  globules  are  discernible  by  the  microscope.  Often  a  few 
uric  acid  crystals  may  be  seen.  The  filaria  has  been  found 
in  the  urine,  but  its  presence  is,  by  no  means,  constant. 


362  DISEASES  OV  THE  URINARY  TRACT. 

The  fat  in  a  chylous  urine  is  in  a  com[)lcte  state  of  emul- 
sion, and  since  it  can  not  be  seen  microscopically,  i/s  pres- 
ence is  dcteruiiiicd  with  certainty  only  by  shaking  with  ether. 
The  ether  takes  up  the  fat  and  leaves  the  urine  clear  and 
of  normal  appearance.  The  fat  does  not  separate  from  a 
freshly  passed  chylous  urine,  or  one  that  has  been  hermeti- 
cally sealed  or  is  sterile — that  is,  the  fat  does  not  rise  to 
the  surface  as  in  the  case  of  milk.  Dr.  E.  S.  Wood  has  in 
his  possession  a  specimen  of  chylous  urine  that  he  sealed 
up  while  it  was  fresh  (sterile)  in  the  year  1874.  The  fat 
has  not  separated  and  the  specimen  has  its  original  appear- 
ance. When,  however,  a  urine  containin<j  chyle  is  allowed 
to  stand  exposed  to  the  air,  it  undergoes  the  usual  ammo- 
niacal  fermentation  and  the  fat  rapidly  separates,  rising  to 
the  surface,  as  in  milk. 

Sometimes  a  chylous  urine  undergoes  spontaneous  co- 
agulation on  standing  ;  occasionally,  coagulation  takes 
place  in  the  bladder,  and  may  give  rise  to  most  distressing 
symptoms  until  it  is  broken  up  and  removed.  The  firm, 
vibrating,  jelly-like  clots  that  form  after  the  urine  is  voided 
often  resemble  corn-starch  bianc  mange.  This  characteris- 
tic of  a  chylous  urine  is  dependent  upon  the  presence  of 
fibrin,  the  quantity  of  which  varies  considerably  ;  usually, 
it  is  not  present  in  sufficient  amount  to  cause  coagulation. 

A  chylous  urine  should  always  be  distinguished  from  a 
urine  to  which  milk  has  been  added  either  accidentally  or 
intentionally.  In  such  a  urine  the  individual  globules  of 
fat  are  readily  made  out  under  the  microscope,  and  the  fat 
is  not  separated  from  the  urine  by  shaking  it  with  ether. 

HEMOGLOBINURIA. 

Hemoglobinuria  is  a  condition  that  is  characterized  by 
the  presence  of  blood  coloring-matter  in  the  7irine,  with  very 
few,  if  any,  of  the  corpuscidar  elements  of  the  blood.  This 
condition  should  in  all  instances  be  distinguished  from  a 
hematuria  which  indicates  the  presence  of  both  blood  pig- 
ment and  corpuscular  elements.  (See  p.  232.)  Hemo- 
globinuria is  the  result  of  the  destruction  of  the  red  blood- 
corpuscles  within  the  blood-vessels  or  tissues  ;  the  blood 
coloring-matter  that  is  then  set  free  finds  its  way  into  the 
urine.  The  blood  pigment,  as  found  in  the  urine  under 
these  circumstances,  is  generally  in  the  form  of  oxyhemo- 


HEMOGLOBINURIA.  363 

globin  and  hematin,  although,  according  to  Hoppe-Seyler  ^ 
and  HalHburton,^  in  some  instances  the  pigment  may  be  in 
the  form  of  methemoglobin  (spectroscopic  examination). 
Two  cHnical  groups  of  this  condition  may  be  distinguished  : 

(a)  Toxic  Hemoglobinuria. — This  is  induced  by  poisons 
that  cause  rapid  destruction  of  the  blood-corpuscles,  such 
as  carbon  monoxide,  arseniureted  hydrogen,  muscarine, 
potassium  chlorate  (in  large  doses)  ;  also  the  poisons  of 
scarlet  fever,  malaria,  yellow  fever,  typhus  fever,  purpura 
hemorrhagica,  scurvy,  and  syphilis.  It  is  quite  common 
following  extensive  burns.  Exposure  to  cold  and  violent 
muscular  exercise  are  stated  to  produce  hemoglobinuria, 
but  such  instances  have  not  been  observed  by  the  author. 
Epidemic  hcnwglobimiria  (Winckel's  disease)  occurs  in  the 
new-born.  It  begins  about  the  fourth  day  of  life,  and  is 
associated  with  jaundice,  cyanosis,  and  nervous  symptoms. 
This  form  of  disease  should  be  distinguished  from  sim- 
ple icterus  neonatorum,  with  which  there  may  be  blood  and 
blood  coloring-matter.  According  to  Osier,  this  condi- 
tion is  probably  an  acute  infectious  disorder. 

(b)  Paroxysmal  Hemoglobinuria. — This  form  of  dis- 
ease has  been  found  in  persons  subject  to  various  forms  of 
Raynaud's  disease.  It  is  also  associated  with  cold  and 
exertion,  and  has  been  brought  on  in  susceptible  persons 
by  the  use  of  a  cold  foot-bath.  This  form  of  hemoglobin- 
uria is  not  infrequent  in  malaria.  According  to  Bastianelli, 
it  practically  never  occurs  except  in  infections  with  the 
estivo-autumnal  parasite.  This  -condition  should  not  be 
mistaken  for  malarial  hematuria. 

The  attacks  may  be  preceded  by  chills  and  fever  ;  in  other 
instances  the  temperature  is  subnormal.  There  may  be 
vomiting  and  diarrhea.  Pain  in  the  lumbar  region  is  not 
uncommon.  Jaundice  has  been  present  in  a  number  of 
cases.  The  paroxysms  rarely  persist  for  more  than  a  day 
or  two.  Paroxysmal  hemoglobinuria  is  more  common  in 
males  than  in  females,  and  occurs  chiefly  during  adult  life. 

Character  of  the  Urine. — Quantity. — This  is  usually 
below  the  normal.  If  much  fever,  the  quantity  may  not 
exceed  500  or  800  c.c. 

Color. — Smoky  or  dark  brown.  In  extreme  cases  the 
urine  may  be  black. 

1  Hoppe-Seyler,  "Physiol.  Chemie.,"  S.  862. 

2  Halliburton,  "Chemical  Physiology  and  Pathology,"  p.  777. 


364  DISEASES  OF  THE  URINARY  TRACT. 

Reaction. — Generally  acid  ;  if  the  urine  is  highly  con- 
centrated, the  reaction   may  be  strongly  acid. 

Specific  Gravity. — Usually,  normal  or  high — from  1020 
to  1030. 

Normal  Solids, — Absolutely,  diminished  ;  the  degree  of 
diminution  will  depend  largely  on  the  disease  that  causes 
the  hemoglobinuria.     Relatively,  increased  or  normal. 

Albumin. — This  varies  between  a  trace  (mild  cases) 
and  y>,  of  I  per  cent,  (severe  cases).  The  quantity  of 
albumin  corresponds  to  the  amount  of  blood  pigment 
present. 

Sediment. — Chiefly  brown  granular  matter,  colored  by 
the  hematin.  An  occasional,  or  few,  brown  and  fine  gran- 
ular, and  often  numerous  brown  granular,  casts.  Rarely, 
an  occasional  blood  globule.  The  number  of  blood 
globules  bears  no  proportion  whatever  to  the  intensity  of 
the  color  of  the  urine.  There  are  usually,  also,  a  {Q.\y 
brown-stained  squamous  and  renal  cells. 

The  diagnosis  of  hemoglobinuria  depends  upon  the  dark- 
brown  color,  the  virtual  absence  of  corpuscular  blood  ele- 
ments, the  large  quantity  of  albumin,  and  the  detection  of 
blood  pigment  by  means  of  Teichmann's  test  (see  p.  235) 
or  the  spectroscope.  Hemoglobinuria  should  always  be 
distinguished  from  hematuria  ;  it  should  not  be  confounded 
with  the  dark-brown  urines  seen  after  the  external  or  inter- 
nal use  of  carbolic  acid,  pyrogallic  acid,  salol,  naphthol,  and 
other  petroleum  compounds,  in  which  the  color  deepens  as 
the  urine  stands  exposed  to  the  air,  and  in  which  the  quan- 
tity of  albumin  is  small.  Hemoglobinuria  should  not  be 
mistaken  for  melanuria,  or  hemotoporphyrinuria.  Spectro- 
scopic examination  is  usually  of  value  in  deciding  as  to  the 
nature  of  the  pigment  present. 


PNEUMATURIA. 

The  passage  of  gas  with  the  urine  is  not  a  common  con- 
dition. Gas  may  gain  entrance  to  the  bladder  by  the  fol- 
lowing means:  (i)  From  mechanical  causes,  as  vesical 
irrigation  or  cystoscopic  examination  in  the  knee-chest  posi- 
tion. (2)  By  developing  in  the  viscus,  follow^ing  the  intro- 
duction of  gas-forming  organisms  in  catheterization  or  other 
operations.  The  yeast  fungus,  the  colon  bacillus,  and  the 
bacillus   aerogenes   capsulatus   have    been  found.     (3)  By 


UREMIA.  S65 

communication  with  some  air-holding  viscus,  as  in  cases  of 
vesico-enteric  fistula. 

Most  cases  of  pneumaturia  occur  in  old  men  with  enlarged 
prostates,  or  in  case  of  obstruction  from  stricture  of  the  ure- 
thra. The  passage  of  the  gas  is  usually  at  the  end  of  mic- 
turition, and  sometimes  may  be  accompanied  by  a  loud 
sound.  The  diagnosis  is  readily  made  by  causing  the  pa- 
tient to  urinate  while  bathing  or  by  plunging  the  end  of 
the  catheter  in  water. 

UREMIA. 

A  toxemia  developing  in  the  course  of  nephritis  or  in 
conditions  associated  with  anuria,  usually  results  in  a  train 
of  symptoms  that  have  received  the  name  uremia.  The 
nature  of  the  poison  or  poisons  that  produce  these  symp- 
toms is  as  yet  unknown. 

Many  theories  as  to  the  cause  of  uremia  have  been  ad- 
vanced. The  view  most  widely  held  is  that  the  condition 
is  due  to  the  accumulation  in  the  blood  of  waste  substances 
— body  poisons — that  should  be  thrown  off  by  the  kidneys. 
As  Carter  has  said,  "  If,  however,  from  any  cause,  these 
organs  [the  kidneys]  make  default,  or  if  there  be  any  pro- 
longed obstruction  to  the  outflow  of  urine,  accumulation  of 
some  or  of  all  the  poisons  takes  place,  and  the  characteristic 
symptoms  are  manifested  ;  but  the  accumulation  may  be 
very  slow,  and  the  earlier  symptoms,  corresponding  to  the 
comparatively  small  dose  of  poison,  may  be  very  slight ; 
yet  they  are  in  kind,  though  not  in  degree,  as  indicative 
of  uremia  as  are  the  more  alarming  symptoms,  which  ap- 
pear toward  the  end,  and  to  which  alone  the  name  uremia 
is  often  given." 

Another  view  is  that  uremia  depends  on  the  products  of 
abnormal  metabolism.  Hughes  and  Carter  concluded,  from 
a  careful  study  of  this  question,  that  the  poison  is  of  an  albu- 
minous nature  ;  in  fact,  quite  different  from  anything  found 
in  normal  urine.  Herter  and  others  have  shown  that  the 
toxicity  of  the  blood-serum  in  uremic  states  is  much  in- 
creased. Brown-Sequard  suggested  that  the  kidneys  have 
an  internal  secretion,  and  it  is  urged  that  the  symptoms  of 
uremia  are  due  to  their  disturbance.  Traube  believed  that 
the  symptoms  of  uremia,  particularly  coma  and  convul- 
sions, were  due  to  localized  edema  of  the  brain. 

It  is  safe  to  say  that  we  know  practically  nothing  of  the 


366  DISEASES  OF  THE  URINARY  TRACT. 

cause  of  uremia.  Experiments  have  shown  that  urea  is 
probably  not  a  causative  agent ;  but  how  much  the  other 
urinary  salts  and  the  nitrogenous  extractives  have  to  do 
with  the  condition  has  not  yet  been  determined.  Bouchard 
claims  to  have  separated  from  the  urine  no  less  than  seven 
different  substances  that  play  a  part  in  uremia  : 

1 .  Diuretic  substance  :  fixed,  organic,  and  in  reality  urea. 

2.  Narcotic  substance  :  fixed,  and  of  organic  nature. 

3.  Sialogenous  substance  :  organic  ;  chemic  nature  un- 
known. 

4  and  5.  Two  substances  causing  convulsions  :  one  (4) 
may  belong  to  the  group  of  coloring-matters  ;  it  is  in  reality 
an  alkaloid.      The  other  (5)  is  the  potassium  salts. 

6.  A  substance  causing  contraction  of  the  pupil  :  fixed, 
organic,  and  comparable  in  many  respects  to  the  organic 
substance  that  induces  convulsions. 

7.  A  substance  that  reduces  heat :   fixed  and  organic. 
Bouchard's   observations   tend   strongly  to    confirm   the 

view  now  generally  held  that  the  symptoms  are  caused  by 
the  retention  of  excretory  products  of  the  body.  It  must 
be  conceded  that  the  nature  of  these  poisonous  ingredients 
is  complex. 

Prominent  Symptoms. — From  a  clinical  point  of  view, 
uremia  may  be  either  acute  or  chronic.  The  division  of  the 
symptoms  as  given  by  the  French  writers  is  perhaps  most 
practical,  and  is  as  follows:  (a)  cerebral ;  {U)  dyspneic  ;  (r) 
gastro-intestinal . 

Among  the  cerebral  manifestations  are  (i)  mania;  (2) 
delusional  insanity;  (3)  convulsions;  (4)  coma  ;  (5)  local 
palsies  ;  and  a  variety  of  nervous  phenomena,  such  as 
occipital  headache,  intense  itching  of  the  skin,  numbness 
and  tingling  in  the  fingers,  and  cramps  in  the  muscles  of 
the  legs. 

Dyspnea. — This  may  be  paroxysmal  or  continuous,  and 
there  may  be  Cheyne-Stokes  breathing. 

The  gastro-intestinal  manifestations  are  usually  chiefly 
nausea  and  vomiting  ;  the  latter  may  be  almost  uncontrol- 
able.  Diarrhea  may  be  present ;  sometimes  it  is  profuse 
and  associated  with  an  intense  catarrhal  or  even  diphtheric 
inflammation  of  the  colon. 

Urine. — An  examination  of  the  urine  is  of  the  greatest 
value  in  the  diagnosis  of  uremia.  The  quantity  of  urine  is 
usually  much  diminished ;  there  may  be  almost  complete 


UREMIA.  367 

suppression.  On  the  other  hand,  the  quantity  may  be  nor- 
mal or  even  increased.  In  a  case  of  chronic  interstitial 
nephritis  studied  by  the  author  at  the  Boston  City  Hos- 
pital, uremic  symptoms  rapidly  developed  when,  for  any 
reason,  the  quantity  fell  from  3500  or  4500  c.c.  down  to 
2000  c.c. 

The  normal  solids  are  usually  diminished,  especially 
the  urea,  but  they  may  be  normal  or  only  slightly  reduced. 
As  a  rule,  the  activity  of  the  symptoms  bears  an  inverse 
ratio  to  the  quantity  of  urea  excreted.  Albuuiin  is  always 
present  in  the  urine  in  this  condition.  It  may  vary  be- 
tween the  slightest  possible  trace  and  3  or  5  per  cent.,  but 
the  quantity  will  depend  upon  the  nature  of  the  associated 
lesion.  The  author  has  not  met  with  a  single  instance  of 
uremia  in  which  albumin  w^as  not  present,  at  least,  in  the 
slightest  possible  trace.  The  sediment  invariably  contains  ab- 
normally formed  elements,  particularly  renal  casts  and  renal 
cells.  It  may  contain  a  variety  of  other  abnormal  elements, 
such  as  blood,  pus,  and  ciystaUine  elements.  Waxy  casts 
are  very  common  in  the  sediment,  especially  when  the 
condition  accompanies  advanced  chronic  disease  of  the 
kidneys. 

Uremia  may  occur  during  either  an  acute  or  chronic 
kidney  disease.  An  acute  exacerbation  of  a  subacute  or 
chronic  nephritis  is  very  liable  to  be  followed  by  uremic 
symptoms.  So  far  as  the  author  is  aware,  uremia  never 
occurs  during  the  course  of  a  simple  active  hyperemia. 

Puerperal  eclampsia,  a  common  complication  arising 
before,  during,  or  after  confinement,  in  all  probability  is 
identical  with  uremia.  It  may  occur  in  the  course  of  an 
extensive  passive  hyperemia  of  pregnancy,  or  as  the  result  of 
a  sudden  acute  nephritis.  A  woman  who  has  had  a  per- 
fectly normal  pregnancy  may  suddenly  develop  uremia 
(eclampsia)  without  previous  warning  either  in  the  urine  or 
by  physical  signs.  No  doubt  puerperal  eclampsia  is  the 
result  of  a  toxemia,  and  it  may  have  the  same  cause  or 
causes  as  uremia. 

Diagnosis. — Uremia  should,  in  ever>^  instance  possible, 
be  distinguished  from  cerebral  lesions,  such  as  hemorrhage, 
meningitis,  and  even  tumors;  also  epilepsy,  acute  alcoholism, 
opium-poisoning,  and  diabetic  coma.  For  information  re- 
garding the  differential  diagnosis  of  uremia,  the  reader  is 
referred  to  various  works  on  medicine. 


368  THE  URINE  IN  GENERAL  DISEASES. 


DIABETES  MELLITUS. 

Diabetes  mellitus  is  a  disease  in  which  grape-sugar  or 
glucose  is  excreted  in  the  urine  for  a  long  period, — often  for 
many  months  or  years, — and  excreted  in  large  quantity  or 
in  sufficient  amount  to  give  a  reaction  with  the  ordinary 
clinical  tests  for  sugar.  But  the  term  diabetes  mellitus  can 
not  be  applied  to  all  cases  in  which  sugar  is  detected  in  the 
urine.  Glucose  is  occasionally  present  in  the  urine  for  a 
short  period  only,  as  after  febrile  attacks,  acute  diseases,  and 
injuries,  and  as  a  result  of  the  action  of  certain  toxic  sub- 
stances. These  are  cases  of  tonporaiy  glycosuria,  and  not  true 
diabetes  mellitus.  Then,  again,  after  a  very  large  quantity 
of  saccharine  food  has  been  taken  a  small  amount  of  grape- 
sugar  may  appear  in  the  urine  of  many  apparently  healthy 
persons,  or  if  the  sugar  in  the  diet  should  exceed  a  certain 
limit,  a  small  quantity  of  it  will  always  be  found  in  the 
urine  ;  these  are  instances  of  temporary  alimentary  glycosu- 
ria (Williamson). 

Causes. — Hereditary  influences  are  important  ;  instances 
are  on  record  of  its  occurrence  in  many  members  of  the 
same  family.  Males  are  more  frequently  affected  than 
females,  the  ratio  being  about  three  to  two  ;  this  is  especially 
true  after  the  age  of  thirty.  In  the  early  period  of  life,  and 
before  the  age  of  thirty,  the  liability  of  the  two  sexes 
is  about  equal.  The  disease  may  occur  in  infancy — under 
one  year — or  in  extreme  old  age.  Hebrews  are  especially 
prone  to  this  disease.  It  is  comparatively  rare  in  the 
colored  race  (from  8  to  lo  per  cent,  Futcher).  In  most 
of  the  cases  of  diabetes  after  thirty  years  of  age  the  subjects 
have  been  excessively/"^/  at  the  beginning  of,  or  prior  to, 
the  onset  of  the  disease.  The  so-called  "  fat  man's  diabe- 
tes "  is  not  of  grave  significance,  since  it  is  usually  the 
result  of  excesses  of  starchy  and  saccharine  diet,  and  is  only 
occasionally  followed  by  true  diabetes.  Von  Noorden  has 
shown  that  there  may  be  a  "  diabetogenous  obesity,"  in 
which  diabetes  and  obesity  develop  in  early  life  ;  such 
cases  are  very  unfavorable.  Gout,  syphilis,  and  malaria 
have  been  regarded  as  predisposing  causes.  Severe  nervous 
strain  and  nervous  shock  precede  many  cases.  In  one 
instance  seen  by  the  author  a  true  diabetes  followed  severe 
fright  at  the  sight  of  a  snake.  The  combination  of  seden- 
tary life,  close  application  to  business,  and  overindulgence  in 


DIABETES  AIELLITUS.  369 

food  and  drink  seem  especially  prone  to  induce  the  disease. 
Injury  to,  or  disease  of,  the  brain  and  spinal  cord  is  not  in- 
frequently followed  by  diabetes.  In  an  investitjation  of  212 
cases  of  traumatic  glycosuria  by  Higgins  and  Ogden  ^  the 
following  results  were  noted  :  In  cases  of  scalp  wounds  and 
minor  head  injuries  glycosuria  was  found  in  5.95  percent.;  in 
scalp  wounds  with  exposure  of  bone,  9.3  per  cent;  in  con- 
cussion, 2.5  per  cent.;  in  fractures  of  the  vault  of  the 
skull,  20.8  per  cent.;  and  in  fractures  of  the  base,  23.8  per 
cent.  From  the  examination  of  these  212  cases  the  follow- 
ing conclusions  were  drawn  : 

1.  That  sugar  may  appear  in  the  urine  as  early  as  six 
hours  after  a  head  injury,  and  disappear  within  twenty-four 
hours  ;  the  average  time  for  its  appearance  being  from  eight 
to  twelve  hours ;  the  average  time  for  its  disappearance 
being  from  the  fifth  to  the  ninth  day. 

2.  That  a  small  proportion  of  cases  exhibit  a  permanent 
glycosuria  from  the  date  of  the  injury  to  the  head. 

3.  That  acetone  and  diacetic  acid  are  rarely,  if  ever,  found 
in  such  cases,  excepting  when  the  condition  becomes  a  per- 
manent glycosuria,  and  even  then  probably  only  after  a 
number  of  months  or  years. 

Glycosuria  may  occur  during  pregnancy.  An  irritative 
lesion  of  Bernard's  diabetic  center  in  the  medulla  is  an  occa- 
sional cause.  Glycosuria  sometimes  occurs  during  the 
course  or  following  acute  infectious  diseases. 

Hibbard  and  Morrissey  ^  found  in  the  observations  made 
on  230  diphtheria  cases  that  glycosuria  was  present  in  25 
per  cent,  of  all  cases  examined ;  in  17  per  cent,  of  the  fatal 
cases,  and  in  19  per  cent,  of  those  that  recovered.  The 
quantity  of  sugar  in  these  cases  varied  between  a  mere  trace 
and  3^  per  cent.  The  time  of  the  appearance  of  the 
glucose  in  the  urine  varied  from  the  second  to  the  eighteenth 
day,  and  the  duration  varied  from  one  day  to  several  weeks. 
The  authors  concluded  that,  in  many  instances,  antitoxine 
was  the  probable  cause  of  the  glycosuria. 

A  glycosuria  sometimes  makes  its  appearance  just  before 
death  in  cases  of  chronic  diffuse  nephritis  and  subacute 
glomerular  nephritis.  It  appears  to  be  in  some  way  con- 
nected with  the  extensive  dropsy  at  this  time,  and  is,  per- 
haps, the  result  of  edema  of  the  brain. 

^  "Boston  Medical  and  Surgical  Journal,"  Feb.  28,  1895. 
2  "Journal  of  the  Boston  Society  of  Medical  Sciences,"  Feb.,  1898. 
24 


370  THE  URINE  IN  GENERAL  DISEASES. 

Lesions  of  the  pancreas  are  met  with  in  about  50  per  cent, 
of  the  cases  (Hansemann).  Total  extirpation  of  this  organ 
in  dogs  has  been  shown  by  v.  Mering  and  Minkowski  to  pro- 
duce diabetes  ;  the  same  result  follows  the  complete  removal 
of  the  pancreas  in  man.  In  disease  of  the  pancreas  diabetes  is 
supposed  to  be  caused  by  the  prevention  of  the  formation 
of  the  glycolytic  ferment.  It  is  believed  that  this  ferment, 
which  emanates  from  the  pancreas,  is  taken  up  by  the  blood, 
and  that  it  is  by  its  presence  alone  that  the  normal  assimi- 
lative processes  can  take  place  with  the  glycogen. 

The  nature  of  diabetes  mellitus  is  unknown.  For  a  sum- 
mary of  the  anatomic  changes  found  in  this  disease,  the 
reader  is  referred  to  Saundby's  "  Lectures  on  Diabetes," 
1891. 

Character  of  the  Urine. — Quantity. — This  is  usually 
greatly  increased,  the  increase  being  generally  in  direct  ratio 
to  the  quantity  of  sugar  present.  In  the  average  case  the 
quantity  varies  from  3000  c.c.  to  6000  c.c.  In  very  severe 
cases  it  may  go  as  high  as,  or  even  exceed,  10,000  or 
20,000  c.c,  in  twenty-four  hours.  Occasionally,  the  total 
daily  quantity  is  less  than  1500  c.c.  This  is  particularly 
true  in  the  very  mild  forms  of  temporary  glycosuria,  or  near 
the  fatal  termination  of  cases  of  true  diabetes  mellitus. 

Color. — Usually,  VQ.xy  pale.  Watery.  Sometimes  the 
urine  has  a  normal,  or  rarely  a  high,  color.  On  standing 
diabetic  urine  speedily  becomes  opalescent,  owing  to  the 
rapid  development  of  yeast  spores  and  other  fungi. 

Reaction. — Generally  acid.  It  is  often  strongly  acid, 
and  the  acidity  increases  at  the  onset  of  diabetic  coma 
(Williamson).  When  a  diabetic  urine  is  allowed  to  stand, 
it  remains  acid  for  many  days,  and  it  may  even  increase  in 
acidity,  owing  to  the  development  of  lactic  acid  by  ferment- 
ation. 

Specific  Gravity. — This  is  increased  ;  it  generally  ranges 
between  1025  and  1050,  or  it  may  be  higher  still.  Not  in- 
frequently the  specific  gravity  is  below  1020.  While  the 
density  of  the  urine  is  raised  if  a  large  quantity  of  sugar  be 
present,  we  can  not  conclude,  if  the  specific  gravity  be  low, 
that  sugar  will  be  absent ;  the  urine  should  be  tested  for  sjigar 
in  every  instance,  tvhether  it  lias  a  high  or  a  low  specific 
gravity. 

Normal  Solids. — Absolutely,  increased,  or  they  may  be 
normal.      Occasionally,  the  total  urea  goes  as  high  as  60  or 


DIABETES  MELLITUS.  371 

lOO  grams.  Owing  to  the  large  quantity  of  urine,  the 
normal  solids  are  relatively  diminished.  In  very  mild  cases 
with  a  small  quantity  of  sugar  they  may  be  relatively 
normal. 

Preceding  or  during  diabetic  coma  the  normal  solids  are 
usually  both  relatively  and  absolutely  diminished. 

Under  ordinary  conditions  the  total  solids  of  the  urine  are 
high,  owing  to  the  presence  of  the  sugar. 

Sugar. — The  presence  of  sugar  is,  of  course,  the  most 
important  abnormality  of  the  urine  in  diabetes.  The  per- 
centage varies,  according  to  the  nature  of  the  case,  from 
0.5  up  to  8  or  12.  The  daily  quantity  of  sugar  also  varies. 
It  is  often  from  20  to  60  grams  in  the  twenty -four  hours,  but 
may  rise  to  300  or  500  grams.  In  rare  instances  the  total 
quantity  of  glucose  may  exceed  750  grams. 

To  estimate  the  amount  of  sugar,  the  total  quantity  of 
urine  for  twenty-four  hours  must  be  carefully  collected  and 
well  mixed,  and  then  a  sample  submitted  to  examination. 
The  twenty-four-hour  excretion  of  sugar  should  be  calculated 
in  all  cases,  since  it  is  by  this  means  only  that  definite  infor- 
mation regarding  the  effect  of  treatment  is  obtained. 

The  twenty-four-hour  quantity  of  urine  should  always  be 
accompanied  by  a  specimen  of  the  fasting  urine  (early  morn- 
ing urine)  ;  also  by  a  specimen  passed  after  the  heartiest 
meal.  A  very  small  amount,  or  an  entire  absence,  of  sugar 
in  the  fasting  urine  constitutes  an  important  element  in  the 
diagnosis  between  a  temporary  glycosuria  and  a  true  dia- 
betes mellitus. 

Albumin. — This  is  usually  present,  but  in  very  small 
amount — generally  the  slightest  possible  trace.  In  case  there 
is  a  coexisting  chronic  interstitial  nephritis,  which  is  not 
very  common,  the  amount  of  albumin  may  reach  a  trace  or 
large  trace. 

Sediment. — An  occa.sional  hyaline  and  finely  granular 
cast  ;  rarely  a  renal  cell  and  blood  globule.  There  is 
usually,  also,  a  moderate  excess  of  squamous  epithelium 
and  sometimes  a  slight  excess  of  leucocytes.  If  the  urine 
has  been  allowed  to  stand  for  some  period,  an  abundance 
of  sugar  spores  (torula  cerevisiae)  will  be  found. 

The  nature  of  the  renal  disturbance  in  the  majority  of 
cases  of  diabetes  mellitus  is  a  renal  congestion  (active  hy- 
peremia), which  is  probably  partly  caused  by  the  irritating 
action  of  the  sugar  on  the  renal  epithelium,  and  possibly  by 


372  THE  URINE  IN  GENERAL  DISEASES. 

the  ingestion  of  an  unusual  amount  of  nitrogenous  food. 
But  a  chronic  nephritis  (usually  the  interstitial  form). is 
sometimes  met  with,  especially  in  those  cases  of  permanent 
diabetes  that  have  been  in  progress  for  several  years.  Un- 
der these  circumstances  the  quantity  of  albumin  is  some- 
what higher,  the  number  of  casts  larger,  and  the  normal 
solids  lower  than  in  the  average  case  of  diabetes  attended 
with  a  renal  congestion. 

Prominent  Symptoms. — In  temporary  glycosuria  symp- 
toms may  be  slight  or  entirely  wanting.  Usually,  polyuria 
is  the  most  noticeable  sign  of  the  condition.  A  hearty  ap- 
petite and  gastric  disorders  are  not  uncommon.  A  craving 
for  sweets  is  sometimes  present.  The  patients  are,  as  a 
rule,  obese  and  past  the  age  of  thirty.  Occasionally,  the 
symptoms  in  this  form  quite  closely  resemble  those  asso- 
ciated with  true  diabetes  mellitus,  but  usually  they  are 
milder  than  in  the  permanent  form  of  the  disease. 

In  permanent  diabetes  the  most  prominent  symptoms  are 
(i)  a  constant  and  seemingly  unquenchable  thirst,  (2)  poly- 
uria, (3)  hunger,  (4)  emaciation,  (5)  general  weakness,  and 
(6)  a  variety  of  nervous  disorders.  Although  the  quantity 
of  water  taken  is  frequently  excessive,  the  tongue  and  mouth 
remain  dry,  parched,  and  congested.  Sometimes  the  gums 
are  tender  and  become  shrunken  so  that  the  teeth  loosen  ; 
frequently,  the  saliva  is  scanty.  The  skin  is  dry  and  harsh. 
Eczema  and  erythema,  especially  about  the  genital  organs, 
are  frequent  and  annoying  symptoms.  Boils  and  carbuncles 
are  among  the  most  common  of  the  skin  lesions  in  diabetes. 
They  often  occur  at  an  early  stage,  and  sometimes  are  the 
first  symptoms  noticed  by  the  patient. 

The  temperature  may  be  normal  or  subnormal.  In  ad- 
vanced cases,  and  especially  preceding  or  during  diabetic 
coma,  the  temperature  may  be  as  low  as  95°  or  94°  F. 
As  a  result  of  the  voracious  appetite,  the  digestion  sooner 
or  later  becomes  disordered.  Constipation  and  attacks  of 
diarrhea  are  not  uncommon  ;   constipation  is  the  rule. 

Various  nervous  manifestations  appear,  such  as  neuralgia, 
neuralgic  pains  in  the  chest,  pain  and  tenderness  in  the 
calves  of  the  legs  (neuritis),  sometimes  sufficient  to  inter- 
fere with  walking.  Sensations  of  abnormal  heat  of  the 
skin  are  common.  The  patient  becomes  fretful,  irritable, 
and  hypochondriacal,  and  usually  there  is  a  marked  lessen- 
ing or  a  complete  loss  of  sexual  power.      Gangrene  of  the 


DIABETIC  COINIA.  373 

extremities  is  common,  especially  in  those  past  the  age  of 
from  thirty  to  forty  years.  Cataract  and  diabetic  retinitis 
are  liable  to  occur. 

The  pronounced  and  persistent  polyuria  produces  fre- 
quent micturition,  which  harasses  the  patient  both  day  and 
night.  The  quantity  of  urine  passed  during  the  day  usu- 
ally exceeds  that  passed  at  night.  One  of  the  most 
frequent  lung  complications  is  tubercular  disease,  which  is 
most  common  in  poor,  hard-working  people.  Cardiac 
weakness  and  enlargement,  sometimes  attended  by  valvular 
disease  or  functional  disturbances,  are  not  uncommon. 

Diagnosis. — An  effort  should  be  made  in  all  cases 
to  distinguish  between  a  permanent  diabetes  niellitiis  and  a 
temporary  glycosuria.  In  both  forms  the  sugar  eliminated 
must  be  glucose  (grape-sugar).  In  the  former  the  sugar  is 
co7istantly  present  in  the  urine,  while  in  the  latter  the  fasting 
urine  (early  morning  urine)  is  generally  free  from  sugar,  or 
contains  only  a  very  slight  trace,  and  the  after-meal  urine  is 
highly  saccharine.  A  diet  free  from  carbohydrates  will 
often  serve  to  distinguish  between  these  two  forms,  since  in 
a  temporary  glycosuria  the  urine  is  usually  quite  readily 
rendered  sugar-free,  while  in  the  permanent  form  the  quan- 
tity of  sugar  may  be  reduced,  but  the  urine  is  made  sugar- 
free  only  with  great  difficulty,  or  not  at  all. 

Course  and  Prognosis. — In  children  the  disease  is  rapidly 
fatal.  It  may  be  stated  that  the  older  the  patient  at  the 
time  of  the  onset,  the  slower  the  course.  In  fleshy  elderly 
individuals,  the  disease  is  much  more  amenable  to  treat- 
ment than  in  thin  persons.  Cases  without  hereditary  influ- 
ences are  the  most  favorable.  Persons  are  met  with  who 
have  had  the  disease  for  fifteen  years  (Osier).  In  true  dia- 
betes mellitus  instances  of  cure  are  rare.  Not  a  few  of  the 
cases  of  reputed  cures  belong  to  the  class  of  temporary 
glycosuria.  In  cases  under  thirty  to  forty  years  of  age  the 
outlook  is  bad. 

DIABETIC  COMA. 

Apart  from  coma  produced  by  various  conditions,  such 
as  cerebral  hemorrhage,  uremia,  etc.,  there  is  a  special  group 
of  symptoms  ending  in  coma  that  is  a  frequent  termination 
of  diabetes.  These  symptoms  are  unaccompanied  by  any 
gross  lesions  of  the  organs,  and  are  apparently  due  to  the 
toxic  condition  of  the  diabetic  blood.     Generally,  the  patient 


374  THE  URINE  IN  GENERAL  DISEASES. 

comes  under  treatment  for  other  symptoms  of  diabetes 
before  the  onset  of  the  coma ;  occasionally,  the  patient  is 
first  seen  during  the  comatose  stage. 

Diabetic  coma  occurs  both  in  the  severe  and  mild  forms 
of  diabetes,  and  rarely,  if  ever,  in  a  temporary  glycosuria. 
It  may  occur  at  any  age,  but  it  is  very  common  in  young 
persons  and  in  persons  under  middle  life. 

An  exciting  cause  is  sometimes  a  long  railway  journey. 
A  sudden  change  of  diet — from  a  mixed  to  a  rigid  nitrog- 
enous diet — often  appears  to  be  an  exciting  cause  of  dia- 
betic coma  ;  and  it  is  said  that  a  sudden  change  from  a 
rigid  nitrogenous  diet  to  a  mixed  nitrogenous  and  carbo- 
hydrate diet  has  occasionally  been  immediately  followed  by 
coma.  The  opinion  is  gradually  gaining  ground  that  a  highly 
nitrogenous  diet  favors  the  development  of  coma,  especi- 
ally in  the  severe  cases  in  which  the  urine  gives  a  port- wine 
color  with  ferric  chloride  (diacetic  acid  reaction).  In  many 
instances  prolonged  constipation  has  appeared  to  play  some 
part  as  an  exciting  cause,  but  it  is  not  invariably  present. 

Diabetic  coma  appears  to  be  occasionally  precipitated  by 
intercurrent  affections  or  complications,  such  as  bronchitis, 
pleurisy,  pneumonia,  tonsillitis,  carbuncles,  pharyngeal, 
ischiorectal,  or  alveolar  abscesses.  The  administration  of 
anesthetics  and  the  performance  of  surgical  operations  have 
also  figured  occasionally  as  exciting  causes  of  coma.  Rapid 
and  marked  loss  of  weight  sometimes  precedes  the  onset  of 
coma. 

The  symptoms  often  begin  with  lassitude,  epigastric 
pain,  nausea,  and  sometimes  vomiting.  Frequently,  dyspnea 
and  headache  are  early  symptoms.  The  patient  becomes 
anxious,  restless,  or  excited.  Speech  becomes  thick  and 
incoherent,  and  finally  he  becomes  drow'sy,  and  the  drowsi- 
ness gradually  develops  into  coma.  The  pulse  is  rapid  and 
the  tension  is  low  ;  the  heart's  action  is  weak,  but  cardiac 
murmurs  are  not  usually  heard.  The  tongue  is  dry  and 
red,  and  the  face  becomes  pale  and  cold  ;  frequently  there 
is  slight  cyanosis. 

Generally,  the  breath  has  a  peculiar  odor ;  the  urine  also 
has  the  same  smell.  The  latter  has  been  variously  de- 
scribed, most  frequently  perhaps  as  an  odor  resembling 
new-mown  hay  ;  it  has  been  termed  the  acetone  odor.  Con- 
vulsions, as  a  rule,  do  not  occur,  and  in  this  respect  diabetic 
coma  differs  markedly  from  uremia. 


DIABETES  INSIPIDUS.  375 

Bremer's  blood  test  with  methylene-blue  will  often 
serve  to  distinguish  diabetic  coma  from  other  forms  of 
coma. 

Urine. — The  urine  is  diminished  in  quantity  preceding 
and  during  diabetic  coma,  the  color  is  not  so  pale  and  the 
acidity  of  the  urine  is  increased.  There  is  frequently  a 
marked  diminution  in  the  quantity  of  sugar  before  the 
onset  and  during  the  coma.  Usually,  the  quantity  of 
albumin  increases.  The  normal  solids  become  absolutely 
much  diminished.  The  sediment  usually  contains  numer- 
ous hyaline  and  finely  granular  casts  ;  a  few  renal  cells, 
which  are  often  quite  granular  ;  and  an  occasional  blood 
globule. 

The  urine  almost  invariably  gives  the  reactions  for  ace- 
tone and  diacetic  acid.      (See  pp.   172  and  175.) 

Importance  of  Acetone  and  Diacetic  Acid  in  Dia- 
betic Urine. — Acetone  and  diacetic  acid  are  most  com- 
monly found  in  the  urine  of  the  advanced  cases  of  true 
diabetes  mellitus.  In  most  instances  their  presence  is  an 
important  prognostic  element.  Although  the  reactions  for 
both  acetone  and  diacetic  acid  may  be  obtained  in  the  urine 
for  weeks  or  months  without  any  comatose  symptoms 
occurring,  they  certainly  indicate  the  constant  danger  of 
coma.  The  author's  experience  leads  him  to  believe  that 
when  these  reactions  are  obtained,  and  especially  a  marked 
reaction  with  ferric  chloride  (diacetic  acid),  an  unfavorable 
prognosis  is  warranted,  although  in  rare  instances  he  has 
known  both  acetone  and  diacetic  acid  to  disappear  from  the 
urine  as  the  patient  improved  under  treatment.  He  has 
never  met  with  these  two  substances  in  cases  of  temporary 
glycosuria. 

DIABETES  INSIPIDUS. 

This  disease  is  characterized  by  the  elimination  of  very 
large  quantities  of  nonsaccharine  urine  of  low  specific 
gravity.  Willis,  in  1674,  first  recognized  the  distinction 
between  the  saccharine  and  nonsaccharine  forms  of  dia- 
betes. The  disease  is  most  common  in  young  persons — 
between  five  and  thirty  years  of  age.  Males  are  more  fre- 
quently attacked  than  females.  The  affection  may  be  con- 
genital, and  in  a  iew  instances  a  hereditary  tendency  has 
been  noted.  Traumatism,  such  as  injury  to  the  head, 
trunk,  or  limbs,  has   occasionally  been   the  exciting  cause. 


376  THE  URINE  IN  GENERAL  DISEASES. 

The  disease  has  also  followed  sunstroke,  or  violent  emotion, 
such  as  fright ;  also  intracranial  growths  or  other  lesions  of 
the  nervous  system.  It  has  followed  rapidly  the  copious 
drinking  of  cold  water,  or  a  drinking-bout ;  or  has  set  in 
during  the  convalescence  from  acute  disease.  Osier  has 
noted  it  in  several  cases  of  tuberculous  peritonitis. 

Practically  nothing  is  known  of  the  pathology  of  this 
disease.      It  is,  doubtless,  of  nervous  origin. 

Prominent  Symptoms. — The  most  prominent  symptoms 
of  this  disease  are  the  marked  and  never-satisfied  thirst, 
the  elimination  of  enormous  quantities  of  urine,  marked 
emaciation,  and  a  dry,  pinched,  and  dusky  skin.  Excep- 
tionally, the  disease  does  not  appear  to  interfere  in  any  way 
with  the  general  health.  The  appetite  is  usually  not  in- 
creased as  in  diabetes  mellitus.  Death  may  take  place  from 
some  intercurrent  affection.  Spontaneous  cure  may  take 
place. 

Character  of  the  Urine. — Quantity. — This  varies  be- 
tween 5000  c.c.  and  20,000  c.c.  during  the  twenty-four 
hours. 

Color. — Very  pale.      Watery. 

Reaction. — Faintly  acid  or  neutral.  Upon  standing,  the 
urine  soon  becomes  ammoniacal  and  turbid,  and  often  has 
a  rather  offensive,  fish -like  odor. 

Specific  Gravity. — This  is  very  low — usually  betAveen 
looi  and  1005. 

Normal  Solids. — Absolutely,  verj'  much  increased  ;  the 
total  urea  may  exceed  100  grams,  while  the  chlorides,  phos- 
phates, and  sulphates  are  also  ver}'  high.  Relatively,  very 
much  diminished. 

Albumin. — Usually  absent ;  the  urine  may,  however, 
contain  the  slightest  possible  trace  of  albumin,  particularly  in 
cases  of  long  standing. 

Sediment. — Very  slight.  Generally,  it  is  necessary  to 
centrifugalize  the  urine  in  order  to  get  any  visible  sediment. 
It  usually  consists  chiefly  of  cellular  elements — squamous 
epithelium  and  small  round  cells  ;  sometimes  a  leucocyte 
and  blood  globule  are  found.  In  exceptional  cases  renal 
casts  (pure  hyaline)  may  be  found. 

Diagnosis. — Hysteric  polyuria  may  sometimes  simulate 
this  disease  very  closely.  The  amount  of  urine  excreted 
may  be  enormous,  but  there  is  never  a  marked  increase  of 
the  solids,  and  often  only  the  development  of  other  hys- 


DIABETES  INSIPIDUS.  377 

teric  manifestations  may  enable  the  diagnosis  to  be  made  ; 
a  polyuria  from  this  cause  is,  however,  always  transitory. 

In  certain  cases  of  cJwonic  interstitial  nephritis  a  very  large 
quantity  of  urine  of  low  specific  gravity  may  be  passed,  but 
the  usual  low  total  solids,  the  presence  of  albumin  and  of 
hyaline  casts,  and  the  existence  of  heightened  arterial  ten- 
sion, stiff  arteries,  and  hypertrophied  left  ventricle  aid  ma- 
terially in  the  diagnosis.  Occasionally,  in  chronic  interstitial 
nephritis  the  normal  solids  as  well  as  the  quantity  of  urine 
are  very  high,  as  in  a  case  seen  by  the  author  about  four 
years  ago ;  a  child,  age  seven  ;  quantity  of  urine,  from 
6000  to  7000  c.c. ;  specific  gravity,  from  1002  to  1006  ;  urea, 
45  grams  ;  chlorine,  13  grams  ;  PgO.,  55  grams.  On  account 
of  the  absence  of  the  usual  signs  and  symptoms  of  chronic 
interstitial  nephritis  the  case  was  supposed  to  be  one  of  dia- 
betes insipidus,  but  at  the  autopsy  very  small,  red,  granular 
kidneys  were  found. 

The  course  of  diabetes  insipidus  depends  entirely  upon 
the  nature  of  the  primary  trouble.  Sometimes  with  organic 
disease,  either  cerebral  or  abdominal,  the  general  health  is 
much  impaired,  Irt  the  idiopathic  cases  the  affection  has 
been  known  to  persist  for  fifty  years  with  a  fair  degree  of 
health.  Death  usually  results  from  some  intercurrent  affec- 
tion.     Recovery  may  take  place. 


CHAPTER    XI. 

THE  URINE  IN  DISEASES  OUTSIDE  OF  THE 
URINARY  TRACT. 

FEVER  URINE. 

In  acute  febrile  conditions  the  characteristics  of  the  urine 
become  modified  from  the  normal  according  to  the  height 
and  character  of  the  fever  and  the  degree  of  toxemia  or 
altered  metabolism.  During  the  early  stage  of  an  acute 
febrile  disease  the  quantity  of  urine  is  abnormally  small, — 
from  500  c.c.  to  loooc.c, — the  color  is  high,  there  is  a  high 
specific  gravity,  and  an  intensely  acid  reaction.  There  is 
usually  a  considerable  amount  of  sediment ;  often  there  is 
an  abundant  sediment  after  the  urine  cools,  due  to  a  deposit 
of  amorphous  urates.  The  normal  solids  are  both  relatively 
and  absolutely  increased,  especially  the  urea,  which  has 
been  known  to  be  as  high  as  85  grams  in  twenty-four  hours. 
Uric  acid  is  also  usually  increased,  although  the  extent  to 
which  it  is  increased  is  largely  dependent  on  the  disease  that 
causes  the  fever.  The  chlorides  are  always  absolutely  dimin- 
ished. The  phosphates  are  absolutely  diminished  at  first, 
but  later  they  are  increased.  In  a  very  mild  febrile  attack 
albumin  may  be  absent.  In  the  more  severe  febrile  diseases, 
with  high  temperature,  albumin  is  always  present,  vary- 
ing in  amount  from  the  slightest  possible  trace  to  a  trace. 
The  sediment  usually  contains  an  occasional  (or  few)  gran- 
ular and  brown  granular  cast,  some  with  blood  and  renal 
cells  adherent ;  a  few  (or  numerous)  free  renal  epithelial 
cells  ;  and  a  i&w  blood  globules. 

As  the  fever  begins  to  abate,  the  quantity  of  urine  in- 
creases, and  frequently  there  is  polyuria  during  the  conva- 
lescence from  the  febrile  condition.  Although  during  con- 
valescence the  patient  may  be  taking  more  food  than  in 
the  early  stage  of  the  disease,  the  normal  solids  for  the 
twenty-four  hours  will  be  diminished,  owing  to  the  fact  that 

378 


URINE  OF  CHRONIC  DISEASE.  379 

the  food  elements  are  used  to  build  up  those  tissues  that  have 
been  diseased.  As  complete  convalescence  approaches,  the 
quantity  of  urine  falls  to  the  normal,  and  the  solids 
gradually  rise  to  their  normal  quantities.  During  conva- 
lescence the  albumin  and  the  other  abnormal  elements  grad- 
ually disappear  from  the  urine,  and  the  renal  tubules  become 
restored  to  their  normal  condition. 

In  case  the  acute  disease  terminates  fatally  during  the 
acute  stage  the  quantity  of  urea  and  other  solids,  instead  of 
being  high,  will  be  found  to  gradually  diminish  up  to  the 
time  of  death,  and  may,  on  the  last  day  or  two  of  the 
disease,  amount  to  only  5  or  10  grams  in  twenty -four 
hours. 

The  characteristics  of  the  urine  in  acute  febrile  condi- 
tions, as  a  rule,  conform  to  those  of  an  active  hyperemia, 
which  may  be  either  mild  or  severe.  Such  renal  disturb- 
ance is  no  doubt  partly  due  to  the  irritating  action  of  the 
concentrated  urine  itself,  but  is  more  directly  dependent  on 
the  elimination  of  irritating  toxines  developed  during  the  dis- 
ease from  which  the  patient  is  suffering.  Although  the 
renal  affection  usually  begins  as  an  active  hyperemia,  it 
often  becomes  intensified,  and  may  result  in  an  acute  neph- 
ritis. The  extent  of  the  renal  involvement  is  usually  in 
direct  proportion  to  the  degree  of  toxemia. 

/;/  acute  diseases  attended  with  a  serous  exudation  the  char- 
acteristics of  the  urine  differ  somewhat  from  the  preceding. 
The  chlorides  are  diminished  to  a  much  greater  extent  than 
in  an  ordinary  acute  affection  without  exudation,  and,  in- 
deed, they  may  be  absent.  The  urea  is  also  not  so  high 
(although  it  may  still  be  above  the  normal)  as  in  acute  dis- 
ease without  serous  exudation.  In  rare  instances  the  total 
urea  may  be  considerably  diminished,  apparently  as  a  result 
of  the  exudation.      (See  Pneumonia,  p.  383.) 

URINE  OF  CHRONIC  DISEASE  (NOT  RENAL). 

In  many  chronic  affections  of  the  body  in  which  fever  is 
absent,  such  as  cancer,  tuberculosis,  etc.,  the  urine  gener- 
ally has  an  entirely  different  appearance  from  that  found  in 
acute  febrile  diseases. 

The  quantity  is  slightly  below  the  normal — 1000  c.c,  or 
1200  c.c.  ;  the  color  is  usually  pale,  but  it  may  be  normal 
or,  rarely,  slightly  high  ;  the   reaction  is  faintly  acid,  or  it 


380  DISEASES  OUTSIDE  OF  THE   URINARY  TRACT. 

may  be  alkaline.  The  normal  solids  arc  both  relatively  and 
absolutely  diminished,  the  amount  of  diminution  being  depen- 
dent largely  upon  the  appetite,  which  is  generally  more  or 
less  disturbed.  Albumin  is  usually  present,  but  in  very 
small  amount ;  occasionally,  it  is  absent.  The  sediment  is 
liable  to  contain  a  very  few  formed  renal  elements  (casts 
and  renal  cells),  although  they,  too,  may  be  absent.  It 
is,  however,  the  rule  to  find,  at  least,  evidences  of  a  renal 
congestion  (active  hyperemia),  and  sometimes  coexisting 
primary  kidney  disease. 

TYPHOID  FEVER. 

The  quantity  of  urine  is  diminished — 500  c.c,  to  800 
c.c;  the  color  is  very  high  (absolute  increase  of  the  pig- 
ments) ;  the  reaction  is  strongly  acid  ;  the  specific  gravity 
is  usually  very  high — 1030  to  1040  ;  the  normal  solids  are 
relatively  increased.  During  the  first  week  of  the  disease 
the  solids,  except  the  chlorides  and  phosphates,  are  abso- 
lutely increased,  the  former  being  only  slightly  diminished 
while  the  latter  are  usually  much  diminished.  The  quantity 
of  urea  may  go  as  high  as  60  to  70  grams.  The  uric  acid 
is  also  much  increased,  and  the  urine  not  infrequently  con- 
tains a  heavy  deposit  of  amorphous  urates.  Albumin  is 
almost  always  present ;  the  quantity  varies  from  the  slightest 
possible  trace  to  j^  of  i  per  cent.,  the  amount  being 
dependent  on  the  height  of  the  fever,  the  toxemia,  and  the 
nature  of  the  resulting  renal  affection.  Peptone  is  said  to 
be  present  in  the  urine  in  typhoid  fever,  especially  in  the 
more  severe  types  of  the  disease.  The  sediment  is  almost 
certain  to  contain  renal  casts,  an  excess  of  renal  epithelial 
cells,  and  a  variable  quantity  of  blood — usually  a  small 
amount. 

An  active  hyperemia  that  is  more  or  less  severe  is  the 
rule  in  typhoid  fever.  Sometimes  a  genuine  acute  nephritis 
develops  at  the  onset  or  during  the  height  of  the  disease, 
masking  in  many  instances  the  true  nature  of  the  primary 
malady  ;  in  such  cases  the  prognosis  is  always  to  be  con- 
sidered grave.  An  acute  nephritis  developing  during  con- 
valescence from  typhoid  fever  is  quite  common,  but,  as  a 
rule,  not  so  serious  as  when  it  dev^elops  early  in  the  dis- 
ease ;  it  usually  makes  its  appearance  after  the  fall  of  the 
fever.     Convalescence  from  an  acute   nephritis,  which  has 


YELLOW  FEVER.  381 

developed  late  in  typhoid,  is  usually  slow,  but  complete 
recovery  is  the  rule. 

Pyuria  is  a  common  complication  of  the  disease.  The 
pus  is  the  evidence  of  a  cystitis  or  a  pyelitis,  and  in  the 
experience  of  the  author  the  latter  is  the  more  common. 
Under  these  circumstances  the  urine  invariably  has  the 
characteristics  of  a  chronic  cystitis  or  chronic  pyelitis,  and  it 
usually  contains  a  large  number  of  typhoid  bacilli.  Orchitis 
is  occasionally  met  with  during  convalescence  ;  it  is  usu- 
ally associated  with  a  catarrhal  urethritis.  In  pyelitis,  cys- 
titis, or  urethritis  from  this  cause  treatment  with  the  formal- 
dehyde compound  known  as  nrotropin  is  usually  highly 
satisfactory. 

In  the  urine  of  typhoid  fever  the  diazo  reaction  of  Ehrlich 
is  often  obtained.  (See  p.  182.)  The  clinical  value  of  the 
reaction  is  doubtful  ;  it  is  certain  that  its  value  is  lessened 
by  its  occurrence  in  acute  miliaiy  tuberculosis  and  various 
other  diseases  associated  with  high  fever. 

YELLOW   FEVER. 

The  quantity  of  urine  is  much  diminished  from  the  first. 
The  color  is  high  or  dark,  depending  upon  the  amount  of 
blood  present  ;  rarely,  it  is  bloody.  The  specific  gravity  is 
usually  below  the  normal,  but  it  may  be  high.  The  urea  is 
often  relatively  diminished,  but  it  may  be  normal  ;  abso- 
lutely, it  is  much  diminished  ;  sometimes  it  is  totally  absent 
(Purdy).  Although  there  is,  without  doubt,  an  increased 
production  of  urea  during  the  stage  of  fever,  yet,  according 
to>  Cunnisset,  the  elimination  of  urea  is  always  less  than 
normal,  the  degree  of  diminution  being  in  direct  proportion 
to  the  danger  of  the  disease,  and  affording  an  important 
element  in  prognosis.  The  chlorides  are  usually  both  rela- 
tively and  absolutely  diminished.  Albuminuria  is  regarded 
by  Guiteras  as  the  third  characteristic  symptom  of  the 
disease.  In  the  mild  cases  the  amount  of  albumin  is 
usually  small,  but  in  the  severe  cases  the  quantity  of 
albumin  is  large  and  there  may  be  numerous  tube  casts  of 
varioug  kinds,  renal  epithelium,  an  abundance  of  blood,  and 
all  the  evidences  of  a  severe  acute  nephritis.  Or  perhaps 
complete  suppression  of  the  urine  may  supervene,  and 
death  may  occur  in  uremic  convulsions  or  coma  within 
twenty-four  or  thirty  hours.     When  albumin  is  present  in 


382  DISEASES  OUTSIDE  OF  THE  URINARY  TRACT. 

the  urine  on  the  first  day  of  the  disease  and  continues  on 
the  second  day,  Guiteras  states  that  it  indicates  a  severe 
case.      The  urine  frequently  contains  bile. 


TYPHUS  FEVER. 

In  this  disease  the  urine  is  scanty  in  amount  and  highly 
febrile.  It  is  highly  colored  and  strongly  acid.  Occasion- 
ally, it  is  alkaline,  and  has  a  veiy  offensive  odor.  Relatively, 
the  urea  is  increased  ;  absolutely,  much  diminished  ;  leucin 
and  tyrosin  may  take  the  place  of  the  urea,  as  in  acute 
yellow  atrophy  of  the  liver.  The  uric  acid  is  relatively  in- 
creased, and  it  may  be  absolutely  increased,  especially 
during  the  early  stages  of  the  disease.  The  chlorides  are 
both  relatively  and  absolutely  greatly  diminished,  and  may 
be  absent.  Albumin  is  invariably  present,  but  usually  in 
small  amount,  except  in  the  severe  cases  attended  with  acute 
nephritis.  Under  such  circumstances  the  urine  is  bloody 
and  bears  the  other  characteristics  of  an  acute  nephritis. 
(See  p.  294.)  The  proportion  of  cases  in  which  an  acute 
nephritis  occurs  varies  much  in  different  epidemics  ;  its  ex- 
istence, howev'er,  adds  decidedly  to  the  gravity  of  the  case. 
A  true  hemoglobinuria  may  be  seen  in  the  severe  cases.  In 
the  mild  cases  the  characteristics  of  the  urine  are  those  of 
a  severe  active  hyperemia  or  renal  congestion.  The  sedi- 
ment contains  numerous  hyaline  and  granular  casts  and 
renal  cells  ;  also  a  varying  amount  of  blood.  At  the  time 
of  the  crisis  copious  amounts  of  urine  of  low  specific  gravity 
and  pale  color  are  passed.  Retention  of  urine  is  of  fre- 
quent occurrence ;  the  region  of  the  bladder  should  be 
frequently  examined,  and  the  catheter  used  if  required. 


RELAPSING  FEVER. 

In  relapsing  fever  the  urinary  system  is  the  seat  of  varj'ing 
morbid  conditions,  some  of  which  are  of  great  importance  in 
determining  the  prognosis.  Albuminuria  is  present  in  a  very 
large  number  of  the  cases,  and  is  not  necessarily  a  cause  of 
very  serious  alarm.  When,  however,  an  abundant  excretion 
of  albumin  is  accompanied  by  the  presence  of  large  numbers 
of  renal  casts,  renal  cells,  and  much  blood,  the  prognosis  is 
grave.  The  affection  of  the  kidneys  may  vaiy  from  a 
simple   congestion  to   an  actual  acute    nephritis,   the  latter 


PNEUMONIA.  383 

being  sometimes  hemorrhagic  in  character.  Complete  sup- 
pression of  urine  is  sometimes  present.  Hematuria  may  be 
profuse  and  exhausting  ;  it  is  a  grave  comphcation  and  is 
often  followed  by  a  fatal  issue.  Glycosuria  has  been 
observed  during  the  course  of  some  cases. 


PNEUMONIA. 

Early  in  the  disease  the  urine  presents  the  usual  charac- 
teristics found  in  acute  febrile  conditions  attended  with 
exudation.  The  quantity  of  urine  is  very  small — often  less 
than  500  c.c.  ;  the  specific  gravity  is  high — 1030  to  1040; 
the  color  is  very  high,  the  amount  of  pigment  being  both 
relatively  and  absolutely  increased.  The  quantity  of  urea 
is  increased.  In  some  instances  the  urea  is  diminished 
after  the  first  few  days  of  the  disease ;  such  cases  are 
usually  characterized  by  delayed  convalescence,  diarrheal 
attacks,  tuberculosis,  pleurisy  with  effusion,  empyema,  etc. 
The  uric  acid  is  usually  very  much  increased,  especially 
just  after  the  crisis,  and  very  often  the  urine  contains  a 
very  heavy  deposit  of  amorphous  urates,  and  is  colored  a 
carmine,  deep  red,  or  brown. 

The  chlorides  are  very  much  diminished  and  may  be 
entirely  absent,  especially  between  the  third  and  fifth  days 
of  the  disease.  The  reappearance  of  the  chlorine  is  evi- 
dence of  beginning  convalescence — the  beginning  of  the 
absorption  of  the  serous  exudation  from  the  diseased  lung. 
The  chlorine  always  reappears  or  commences  to  increase  in 
quantity  before  evidences  of  beginning  convalescence  can  be 
made  out  by  auscultation  and  percussion  or  by  a  fall  in  the 
temperature. 

Albumin  is  invariably  present  in  pneumonia — often  only 
the  slightest  possible  traee  in  mild  cases,  and  a  large  trace  to 
y%  of  I  per  cent,  in  the  severe  cases.  Sometimes  a  large 
amount  of  albumin  and  a  bloody  or  smoky  urine  indicate 
the  presence  of  an  acute  nephritis.  In  a  large  proportion 
of  all  cases  the  albumin  is  evidence  of  a  more  or  less  severe 
toxic  condition.  According  to  v.  Jaksch,  the  appearance  of 
peptone  in  the  urine  is  indicative  of  the  beginning  of  resolu- 
tion. 

The  sediment  usually  contains  a  few  (or  numerous)  hya- 
line, fine,  and  brown  granular  casts,  numerous  renal  cells, 
and  abnormal  blood  globules.      Blood  may  be   present  in 


384  DISEASES  OUTSIDE  OF  THE  URINARY  TRACT. 

abundance,  when  the  sediment  usually  has  the  other  char- 
acteristics of  an  acute  diffuse  nephritis.      (Compare  p.  294.) 

The  urine  may  contain  bile  pigment. 

During  convalescence  from  pneumonia  the  quantity  of 
urine  increases  and  may  exceed  the  normal  ;  the  quantity 
of  urea  and  uric  acid  return  to,  and  sometimes  fall  below, 
the  average  normal,  while  the  chlorides  gradually  become 
increased,  finally  returning  to  normal. 

PULMONARY  TUBERCULOSIS. 

In  the  average  uncomplicated  case  of  pulmonary  tuber- 
culosis the  urine  does  not  present  any  special  peculiarities. 
The  quantity  is  usually  diminished,  especially  if  there  is 
fever  ;  if  no  fever,  the  quantity  may  be  increased,  even  in 
uncomplicated  cases.  If  amyloid  infiltration  be  present  as 
a  complication,  the  quantity  of  urine  is  usually  increased. 
In  the  average  case  of  pulmonary  phthisis  with  fever  the 
color  of  the  urine  is  higher  than  normal,  the  specific  gravity 
is  moderately  increased,  and  the  reaction  is  strongly  acid. 
The  normal  solids  are  relatively  increased  ;  absohitely,  dimin- 
ished. The  urea  is  usually  diminished,  but  the  extent  of 
the  diminution  is  dependent  on  the  appetite,  the  general 
metabolism,  and  the  fever.  The  uric  acid  is  generally 
increased,  while  the  sulphates  are  only  moderately  dimin- 
ished. The  chlorides  are  usually  somewhat  diminished, 
but  the  quantity  of  chlorine  is  largely  dependent  on  the 
character  of  the  food  taken.  If  there  is  marked  diarrhea, 
the  chlorides  will  be  found  absolutely  very  much  dimin- 
ished. In  some  cases  of  pulmonary  tuberculosis  the  phos- 
phates are  absolutely  increased,  especially  when  the  lung 
tissue  is  breaking  down  rapidly. 

Albumin  is  probably  present  in  the  urine  of  every  case 
of  advanced  phthisis.  As  has  been  stated,  subacute  glomer- 
■  ular  nephritis  and  amyloid  infiltration  are  frequent  compli- 
cations of  pulmonary  tuberculosis.  (See  pp.  301,  318.) 
Under  such  circumstances  the  quantity  of  albumin  is  large. 
If  such  complications  are  not  present,  the  quantity  of  albu- 
min is  usually  small — slightest  possible  trace  to  a  trace. 

The  sediment  usually  contains  an  occasional  (or  a  few) 
renal  cast,  renal  cell,  and  a  very  small  amount  of  blood  ; 
in  other  words,  evidence  of  a  more  or  less  marked  renal 
congestion. 


MALARIAL  FEVER.  385 

Besides  the  liability  of  an  amyloid  infiltration,  or  a  sub- 
acute glomerular  nephritis  as  a  complication,  tubercular 
ulcerations  in  the  kidney,  pelvis  of  the  kidney,  or  the 
bladder  are  very  likely  to  occur.  Pyuria  is  then  the  most 
prominent  feature  of  the  urine.  In  all  such  cases  the 
urinary  sediment  should  be  very  carefully  examined  for 
tubercle  bacilli. 

MALARIAL  FEVER. 

During  the  pyrexia  the  urine  has  the  usual  characteris- 
tics of  a  fever  urine.  The  quantity  is  small,  the  color  is 
high,  and  the  specific  gravity  is  increased.  After  the  chill 
and  the  fever  the  urine  is  often  increased  in  amount  and  of 
low  specific  gravity.  There  is  always  an  increase  in  the 
elimination  of  urea  during  a  paroxysm,  and  Jaccoud  has 
noted  that  this  increase  commences  even  before  the  chill,  so 
that  careful  quantitative  estimations  of  urea  will  often  fore- 
tell the  approach  of  a  paroxysm.  This  increase  of  the 
urea  excretion  he  observed  two  hours  before  the  chill  in 
quotidian,  and  six  or  eight  hours  before  in  tertian,  fever. 
He  regards  the  increased  urea  as  a  reliable  indication  for 
the  proper  time  for  administering  quinine  in  order  to  antici- 
pate the  chill.  During  the  paroxysm  the  chlorine  is  elimi- 
nated in  normal  amount.  On  the  days  between  paroxysms 
both  the  urea  and  chlorine  are  usually  diminished. 

-The  urine  usually  contains  albumin,  but  generally  in 
small  amount — slightest  possible  trace.  If  an  acute  neph- 
ritis develops,  the  quantity  of  albumin  is  large — ^  to  i^ 
of  I  per  cent.  The  sediment  generally  contains  renal  casts, 
renal  cells,  and  a  few  blood  globules.  The  renal  disturb- 
ance is  usually  of  the  nature  of  a  renal  congestion  or  active 
hyperemia. 

An  acute  nephritis  in  malaria  is  not  very  common  in 
New  England.  Thayer,  ^  who  has  recently  made  a  study 
of  the  urine  in  malaria  at  the  Johns  Hopkins  Hospital, 
draws  the  following  conclusions  : 

(i)  Albuminuria  is  of  frequent  occurrence  in  the  malarial 
fevers  of  Baltimore,  occurring  in  46.6  per  cent,  of  the  cases 
studied.  (2)  It  is  considerably  more  frequent  in  estivo- 
autumnal  infections  than  in  the  other  forms,  occurring  in 
58.3  per  cent,  of  these  instances  against  38.6  per  cent,  in 

'  "  Amer.  Journ.  Med.  Sciences,"  Dec,  1898,  p.  646. 
.      25 


386  DISEASES  OUTSIDE  OF  THE  URINARY  TRACT. 

the  regular  intermittent  forms.  (3)  Acute  nephritis  is  not 
an  unusual  complication  of  malarial  fever,  having  occurred 
in  2.7  per  cent,  of  the  cases  treated  in  the  wards  and 
between  i  and  2  per  cent,  of  all  cases  seen  at  the  hospital. 
(4)  The  frequency  of  acute  nephritis  in  estivo-autumnal 
fever  is  much  greater  than  in  the  regular  intermittent  forms, 
having  been  observed  in  4.7  per  cent,  of  the  cases  treated  in 
the  wards  and  in  2.5  percent,  of  all  cases  seen.  (5)  The 
frequency  of  albuminuria  and  nephritis  in  malarial  fever, 
while  somewhat  below  that  observed  in  the  more  severe 
acute  infections,  such  as  typhoid  fever,  scarlet  fever,  and 
diphtheria,  is  yet  considerable.  (6)  There  is  reason  to  believe 
that  malarial  infection,  especially  in  the  more  tropical  coun- 
tries, may  play  an  appreciable  part  in  the  etiology  of  chronic 
renal  disease. 

Paroxysmal  hemoglobinuria  is  sometimes  a  complication 
of  malaria.  Like  an  acute  nephritis,  this  complication  is 
perhaps  more  common  in  the  Southern  States  and  tropical 
countries  than  in  New  England.  Out  of  several  hundred 
cases  of  malarial  fever  at  the  Boston  City  Hospital,  the 
author  has  only  once  met  with  hemoglobinuria.  The  rela- 
tion of  this  condition  to  malaria  is  not  so  close  as  has  been 
thought  by  many  writers.  Bastianelli  asserts  that  it  is 
practically  proved  that  malarial  hemoglobinuria  occurs  only 
in  infections  with  the  estivo-autumnal  parasite.  No  doubt 
it  has  frequently  been  confounded  with  malarial  hematuria. 

Malarial  hematuria  of  renal  origin  is  sometimes  encoun- 
tered, especially  in  the  estivo-autumnal  form  of  the  disease. 
In  such  cases  the  evidences  of  tubular  disturbance  of  the 
kidney  (casts,  renal  cells,  etc.)  is  usually  very  slight. 

ERYSIPELAS. 

In  this  disease  the  urine  is  scanty  in  amount,  highly 
colored,  and  of  high  specific  gravity.  Relatively,  the  solids 
are  all  increased  ;  absolutely,  diminished,  especially  after  the 
first  two  or  three  days  of  the  disease.  Albuminuria  is 
almost  constant ;  usually,  the  quantity  of  albumin  is  small, 
varying  between  a  very  slight  trace  and  a  large  trace.  A 
true  acute  nephritis  is  quite  common  ;  the  quantity  of  albu- 
min may  then  reach,  or  even  exceed,  i  per  cent.  The 
sediment  always  contains  renal  casts,  usually  an  excess  of 
renal  epithelium,  and  a  few  (or  numerous)  blood  globules, 


CHOLERA.  387 

both  free  and  adherent  to  casts.  The  number  of  casts  and 
cellular  elements,  and  the  quantity  of  blood,  may  be  very 
large,  indicative  of  an  acute  nephritis.  In  the  experience 
of  the  author  an  acute  pyelonephritis  in  erysipelas  is  not 
uncommon.  Chronic  pyelitis  is  sometimes  the  result  of 
the  acute  pyelitis  ;  convalescence  from  this  complication  is 
usually  slow.  In  case  the  erysipelas  is  complicated  by 
pneumonia,  ulcerative  endocarditis,  or  septicemia,  a  severe 
acute  pyelonephritis  is  quite  sure  to  follow,  and  the  prog- 
nosis is  thereby  rendered  grave. 


CHOLERA. 

In  the  first  two  or  three  days  of  this  disease — algid  or 
collapse  stage — the  quantity  of  urine  is  very  small,  or 
there  may  be  complete  suppression  ;  the  color  is  normal  or 
pale,  sometimes  smoky  ;  the  specific  gravity  is  either  normal 
or  diminished  ;  and  the  reaction  is  faintly  acid.  The  urea 
is  very  much  diminished  ;  this  marked  diminution  is  un- 
usual in  most  acute  diseases,  and  in  cholera  it  is  prob- 
ably due  to  the  fact  that  a  large  proportion  of  the  urea  is 
eliminated  with  the  intestinal  discharges.  In  case  of  sup- 
pression of  urine  a  considerable  amount  of  urea  may  be 
eliminated  by  the  sweat  glands  ;  indeed,  it  is  sometimes 
eliminated  in  sufficient  quantity  to  cause  a  coating  of  urea 
on  the  skin,  especially  in  the  axillae  and  groins.  The  uric 
acid  is  also  much  diminished.  The  chlorides  are  very  much 
diminished,  or  they  may  be  absent.  The  phosphates  are, 
like  the  urea,  very  much  reduced. 

The  indoxyl — indoxyl-potassium  sulphate — is  much  in- 
creased, and  in  rare  instances  the  urine  has  a  blue  color 
and  contains  a  deposit  of  indigo.  In  early  times,  before 
the  recognition  of  the  cholera  bacillus,  the  high  indoxyl 
was  considered  an  important  element  in  the  diagnosis 
of  cholera.  It  should  be  borne  in  mind,  however,  that  a 
large  increase  in  the  indoxyl  is  frequently  found  in  other 
conditions  than  cholera,  such  as  peritonitis,  intestinal  ob- 
struction, etc.,  so  that  too  much  reliance  can  not  be  placed 
on  a  high  indoxyl  in  the  diagnosis  of  cholera. 

During  the  algid  stage  the  urine  invariably  contains  albu- 
min. The  quantity  varies,  but  it  may  be  large  and  frequently 
indicates  the  presence  of  an  acute  nephritis.  Often  the  albu- 
minuria disappears  with  the  subsidence  of  the  algid  stage. 


388  DISEASES  OUTSIDE  OF  THE  URINARY  TRACT. 

The  sediment  contains  renal  casts,  often  in  large  num- 
bers, many  renal  cells,  and  a  few  (or  numerous)  blood 
globules.  If  an  acute  nephritis,  the  quantity  of  blood  will 
be  large,  and  there  will  be  a  large  number  of  brown  granu- 
lar, blood,  epithelial,  and  fibrinous  casts. 

After  the  third  day,  in  a  favorable  case,  the  quantity  of 
urine  rapidly  increases,  the  color  is  pale,  and  the  specific 
gravity  is  very  low.  Coincident  with  this  increase  of  the- 
urine  there  is  a  rise  in  the  urea,  chlorides,  phosphates,  and 
other  solids.  The  urine  may  temporarily  exceed  the  normal 
— for  example,  it  may  rise  to  60  to  80  grams  and  then 
gradually  return  to  the  normal.  The  chlorides  and  phos- 
phates, however,  do  not,  as  a  rule,  exceed  the  normal.  In 
case  of  an  acute  nephritis  during  the  algid  stage  a  typical 
convalescent  stage  of  acute  nephritis  is  seen  when  the  patient 
begins  to  improve. 

But  the  complication  of  an  acute  nephritis  during  the  col- 
lapse period  may  be  the  direct  cause  of  death  by  uremic 
coma.  In  cholera,  after  the  third  day,  if  the  quantity  of 
urine  does  not  increase,  the  albumin  does  not  diminish,  and 
the  urea  and  chlorine  do  not  begin  to  rise  in  quantity,  the 
prognosis  can  be  considered  very  grave. 


SCARLET  FEVER. 

The  urine  in  this  disease  is  subject  to  much  variation.  It 
is  very  common,  and,  indeed,  the  rule  to  find  evidences  in 
the  urine  of  a  severe  renal  congestion  or  an  acute  nephritis 
(sometimes  the  acute  interstitial  form).  But  in  many  in- 
stances the  kidneys  escape  without  greater  damage  than 
occurs  in  other  acute  febrile  affections.  An  acute  nephritis  is 
most  common  in  the  second  or  third  week  of  the  disease,  and 
may  develop  after  a  very  mild  attack  of  scarlet  fever.  Not 
infrequently,  an  acute  nephritis  makes  its  first  appearance 
late  in  the  period  of  desquamation,  when  it  usually  exists 
in  a  mild  form.  As  a  rule,  the  earlier  it  develops,  the  more 
severe  it  is. 

The  renal  disturbance  varies  greatly  in  intensity,  but  in 
all  instances  during  the  height  of  the  fever  the  urine  is 
diminished  in  quantity  and  of  high  specific  gravity.  It  has 
a  high  or  smoky  color,  an  intensely  acid  reaction,  and  the 
normal  solids  are  relatively  increased,  especially  the  urea 
and  uric  acid  ;   they  are  absolutely  diminished  except  during 


SCARLET  FEVER.  389 

the  first  da}'  or  two  of  the  disease.  If  there  be  dropsy,  the 
chlorides  and  urea  are  very  much  reduced,  especially  the 
former.     Three  distinct  grades  of  cases  may  be  recognized. 

Mild  Cases. — The  urine  has  a  high  color,  and  invariably 
contains  albumin — usually  the  slightest  possible  trace  to  a 
trace.  The  sediment  contains  an  occasional  (or  few)  hyaline, 
granular,  and  brown  granular  casts,  renal  cells,  and  a  few 
blood  globules,  Iree  and  attached  to  casts  ;  in  other  words, 
there  is  evidence  of  a  mild  renal  congestion  or  active  hyper- 
emia. Edema  is  absent,  and  the  convalescence  from  the 
fever  is  scarcely  interrupted. 

Severe  Cases. — The  urine  has  a  smoky  color  and  con- 
tains considerable  albumin — usually  varying  in  amount  be- 
tween a  large  trace  and  y^  of  i  per  cent.  The  sediment 
contains  many  hyaline,  granular,  and  brown  granular,  a  few 
epithelial,  blood,  and  fibrinous  casts  ;  also  many  renal  cells 
and  frequently  small  caudate  cells  from  the  superficial  layer 
of  the  pelvis  of  the  kidney  ;  considerable  altered  blood,  and 
a  few  pus-corpuscles — the  evidences  of  an  acute  pyelo- 
nephritis. Edema,  especially  about  the  eyelids,  is  a  con- 
stant symptom  ;  there  may  be  edema  of  the  feet.  The 
renal  symptoms  then  dominate  the  entire  case.  The  con- 
dition may  continue  and  finally  become  chronic,  but  fortu- 
nately, in  a  majority  of  the  cases,  the  disease  yields  to  judi- 
cious treatment,  and  complete  recovery  takes  place. 

Very  Severe  Cases. — In  this  class  of  cases  there  is 
usually  either  complete  suppression  of  urine  or  the  passage 
of  a  small  quantity  of  very  dark  (almost  black)  urine, 
which  contains  a  high  quantity  of  albumin — from  ^  to 
I  y^  per  cent.  The  sediment  contains  the  same  elements 
that  are  found  in  the  severe  cases,  but  in  much  larger  num- 
bers— a  very  severe  acute  pyelonephritis.  There  is  marked 
dropsy,  vomiting,  and  convulsions,  and  the  child  dies  with 
the  symptoms  of  acute  uremia. 

In  the  favorable  cases  of  acute  pyelonephritis  the  third  or 
convalescent  stage  soon  makes  its  appearance,  when  the 
quantity  of  urine  increases,  the  color  is  very  slightly  smoky 
or  pale,  and  fat  appears  in  the  renal  cells  and  is  found 
attached  to  the  casts.  As  previously  stated,  with  judicious 
treatment  complete  recovery  usually  takes  place.  Occa- 
sionally, convalescence  becomes  prolonged  and  a  chronic 
nephritis  results.  Sometimes  a  marked  chronic  pyelitis  is 
the  result  of  the  acute  pyelitis. 


390  DISEASES  OUTSIDE  OF  THE  URINARY  TRACT. 

The  urine  in  scarlet  fever  should  in  all  cases  be  carefully 
watched,  owing  to  the  fact  that  renal  complications  are 
among  the  most  common. 

DIPHTHERIA. 

In  diphtheria,  as  in  other  acute  infectious  diseases,  renal 
complications  are  common  ;  they  are,  however,  less  common 
than  in  scarlet  fever.  The  quantity  of  urine  is  diminished  ; 
the  color  is  high,  or,  if  an  acute  nephritis,  smoky  ;  the  spe- 
cific gravity  is  high — 1025  to  1035.  Relatively,  the  normal 
solids  are  increased,  but  absolutely,  diminished.  Albu- 
minuria is  a  constant  symptom  in  all  severe  cases,  and,  in 
fact,  albumin  is  present  in  nearly  all  of  the  milder  cases. 
It  varies  in  amount  from  the  slightest  possible  trace  to  a  large 
trace.  If  an  acute  nephritis  develops,  it  may  exceed  y^  of 
I  per  cent.  The  sediment  contains  renal  casts,  renal  cells, 
and  a  small  amount  of  blood  both  free  and  on  casts — evi- 
dences of  an  active  hyperemia. 

An  acute  nephritis  is,  however,  not  uncommon.  It  may 
appear  quite  early  in  the  disease.  Occasionally,  it  begins 
with  complete  suppression  of  urine.  In  comparison  with 
scarlet  fever  the  renal  changes  lead  less  frequently  to  gen- 
eral dropsy.  The  sediment  usually  contains,  besides  brown 
granular,  blood,  epithelial,  and  fibrinous  casts,  many  renal 
cells,  much  blood,  and  numerous  small  caudate  cells  from 
the  pelvis  of  the  kidney — evidences  of  an  acute  pyelo- 
nephritis. The  course  of  the  nephritis  is  usually  favorable. 
Occasionally,  there  are  convulsions,  and  the  patient  dies  from 
acute  uremia.  Sometimes  a  chronic  nephritis  follows  an 
acute  nephritis.  Acute  nephritis  is  a  less  frequent  compli- 
cation of  diphtheria  since  the  advent  of  the  antitoxine  treat- 
ment of  this  disease. 

Hibbard  and  Morrissey  ^  have  found  that  a  glycosuria  is 
not  uncommon  in  diphtheria. 

SMALLPOX. 

In  this  disease  the  urine  has  the  usual  typical  character- 
istics of  fever.  The  quantity  of  urine  is  small,  the  coloring- 
matters  are  increased,  and  the  specific  gravity  is  high. 
Relatively  and  absolutely,  the  urea  is  generally  increased, 
but  it  may,  rarely,  be  absolutely  much  diminished  ;  under 

'  "  Journ.  of  the  Society  of  Med.  Sciences,"  Feb.,  1898. 


ACUTE  GENERAL  PERITONITIS.  391 

such  circumstances,  leucin  and  tyrosin  may  appear  in  the 
urine  instead  of  urea.  The  chlorides,  sulphates,  and  phos- 
phates are  absolutely  somewhat  diminished.  The  uric  acid 
is  increased,  and  the  urine,  on  cooling,  frequently  deposits 
amorphous  urates. 

Albumin  is  invariably  present  in  the  urine  in  all  cases  of 
smallpox,  and  it  generally  makes  its  appearance  with  the 
onset  of  the  disease.  The  sediment  contains  renal  casts, 
renal  cells,  and  a  moderate  amount  of  blood  both  free  and 
adherent  to  casts.  An  active  hyperemia,  which  is  usually 
quite  severe,  is  the  rule.  Occasionally,  a  true  acute 
nephritis  develops,  especially  in  the  malignant  forms.  The 
urine  frequently  contains  bile  pigment.  In  the  hemorrhagic 
form  of  the  disease  hemoglobinuria  may  be  a  prominent 
feature  of  the  urine.  Care  should  be  taken  not  to  confound 
a  hemoglobinuria  with  a  hematuria  accompanying  an  acute 
nephritis. 

ACUTE  GENERAL  PERITONITIS. 

In  this  disease  the  quantity  of  urine  is  very  small,  the 
color  is  high,  and  the  specific  gravity  is  above  the  normal. 
A  prominent  feature  of  the  urine  is  the  very  large  excess  of 
indoxyl.  Relatively,  the  normal  solids  are  increased,  except 
the  chlorides,  which  are  very  much  diminished  or  absent ; 
absolutely,  the  solids  are  diminished.  Albumin  is  generally 
present,  and  in  the  sediment  will  be  found  renal  casts,  renal 
.cells,  and  a  variable  amount  of  blood — in  other  words, 
evidences  of  a  more  or  less  severe  active  hyperemia  of  the 
kidneys. 

In  localized  peritonitis  the  chlorides  are  not,  as  a  rule, 
much  diminished,  if  at  all  ;  the  degree  of  diminution  is, 
however,  dependent  on  the  extent  of  the  pathologic  process 
and  the  amount  of  serous  exudation. 


INTESTINAL  OBSTRUCTION. 

In  this  condition  the  urine  is  small  in  amount,  and  there 
may  be  almost  complete  suppression,  particularly  when  the 
obstruction  is  high  up  in  the  bowel.  This  is  probably  due 
to  the  excessive  vomiting  and  the  small  amount  of  liquid 
taken.  The  urine  has  a  high  color,  and  the  specific  gravity 
is  above  the  normal — 1025  to  1035.  Relatively,  the  solids 
are  increased  ;  absolutely,  diminished.     When  the  obstruc- 


392  DISEASES  OUTSIDE  OF  THE  URINARY  TRACT. 

tion  occurs  in  the  small  intestine,  the  indoxyl  is  usually  very- 
high  ;  in  one  case  the  amount  of  indoxyl  reported  was  as 
high  as  98  milligrams.  Albumin  is  usually  present,  but  in 
small  amount ;  and  the  sediment  contains  renal  casts,  renal 
epithelial  cells,  and  a  little  blood.  In  the  majority  of  cases 
of  intestinal  obstruction  the  renal  disturbance  is  of  the 
nature  of  a  renal  congestion  or  toxic  irritation. 


ACUTE  YELLOW  ATROPHY  OF  THE  LIVER. 

The  twenty-four-hour  quantity  of  urine  is  small,  the  re- 
action is  strongly  acid,  and  the  specific  gravity  is  low.  The 
urine  contains  both  bile  pigments  and  the  bile  acids.  Rela- 
tively and  absolutely,  the  normal  solids  are  much  diminished. 
The  urea  is  present  in  very  small  amount  or  it  may  be 
absent.  Instead  of  the  urea,  leucin  and  tyrosin,  one  or 
both,  are  usually,  although  not  constantly,  present  in  the 
urine ;  of  23  recent  cases  collected  by  Hunter,  in  9  neither 
was  found;  in  10,  both  were  present;  in  3,  tyrosin  only; 
in  I,  leucin  only.  Both  leucin  and  tyrosin  have  character- 
istic crystalline  shapes  (see  pp.  225,  226),  and  are  found  in 
the  urinary  sediment.  In  the  search  for  these  crystals  it  is 
advisable  to  previously  render  the  urine  acid  with  acetic  acid 
and  concentrate  by  evaporation.  The  phosphates  and  uric 
acid  are  very  much  reduced.  The  urine  always  contains 
albumin,  which  may  be  present  in  considerable  quantity — 
^  to  ^  of  I  per  cent.  The  sediment  contains  numerous 
hyaline,  granular,  and  fatty  casts,  fatty  renal  cells,  and 
compound  granule  cells  ;  in  other  words,  the  urine  indicates 
a  more  or  less  marked  fatty  degeneration  of  the  kidneys. 
The  casts  and  renal  cells  are  usually  stained  yellow  by  the 
bile  pigment. 

Acute  yellow  atrophy  is  of  rare  occurrence  and  is  rapidly 
fatal.  It  is  characterized  by  jaundice  and  marked  cerebral 
symptoms,  and  anatomically,  by  extensive  necrosis  of  the 
liver-cells  with  reduction  in  the  volume  of  the  organ.  The 
symptoms  produced  by  phosphorus-poisoning  closely 
simulate  those  of  acute  yellow  atrophy,  but  it  should  be 
borne  in  mind  that  the  two  conditions  are  not  identical. 


HYSTERIA.  393 

HYSTERIA. 

During  and  immediately  following  an  attack  of  hysteria 
the  twenty-four-hour  quantity  of  urine  is  much  increased, 
not  infrequently  going  as  high  as  5000  c.c.  The  color  is 
very  pale  and  watery  ;  and  the  specific  gravity  is  low — 1002 
to  1012  ;  the  reaction  is  faintly  acid.  Relatively,  the  solids 
are  much  diminished  ;  absolutely,  normal  or  only  slightly 
diminished,  and  sometimes  they  are  increased.  The  urine 
is  frequently  free  from  albumin  ;  on  the  other  hand,  it  may 
be  present  in  very  small  amount — slightest  possible  traee. 
The  sediment  usually  contains  only  a  moderate  excess  of 
squamous  epithelial  cells.  If  the  urine  contains  albumin, 
after  centrifugalizing  the  sediment  will  be  found  to  contain 
an  occasional  hyaline  and  finely  granular  cast,  renal  cell, 
and  blood  globule — in  other  words,  evidences  of  a  very 
slight  active  hyperemia,  perhaps  the  result  of  increased 
activity  of  the  kidneys.  Since  hysteria  is  more  common  in 
the  female  than  in  the  male,  the  presence  in  the  urine  of  a 
profuse  vaginal  secretion  will  in  many  instances  account  for 
a  very  slight  albuminuria,  without  necessarily  having  any 
evidence  of  a  renal  disturbance. 

Charcot  has  called  attention  to  the  fact  that  in  hysteria 
the  quantity  of  urine  may  be  very  small.  He  records  a 
case  in  which  the  patient  suffered  from  v^omiting  and  diar- 
rhea, and  in  which  there  w^as  complete  suppression  of  urine 
for  eleven  days.  Deception  was  not  possible,  as  the 
patient  was  closely  watched. 

CEREBROSPINAL  MENINGITIS. 

In  this  disease  the  urine  has  the  characteristics  of  a  fever 
urine  accompanied  by  exudation.  The  quantity  of  urine  is 
small ;  the  color  is  normal  or  pale,  and  sometimes  it  is 
high  ;  the  specific  gravity  is  usually  somewhat  above  the 
normal  ;  and  the  reaction  is  only  faintly  acid  or  it  may  be 
alkaline.  The  total  quantity  of  urea  is  high,  the  increase 
usually  amounting  to  25  per  cent,  or  more  (Purdy).  The 
phosphates  are  much  increased  in  the  early  part  of  the  dis- 
ease, so  that  upon  performing  the  heat  test  for  albumin 
without  the  customary  addition  of  acetic  acid,  an  abundant 
precipitate  is  thrown  down  by  the  test ;  later  in  the  disease 
the    phosphates    become    diminished.     The    chlorides    are 


394  DISEASES  OUTSIDE  OF  THE  URINARY  TRACT. 

greatly  diminished  from  the  first  and  may,  in  rare  instances, 
be  absent.  Albumin,  which  is  invariably  present,  varies  in 
quantity  from  the  slightest  possible  trace  to  ^  or  ^^  of  i 
per  cent.,  but  is  dependent  on  the  amount  of  renal  involve- 
ment and  the  quantity  of  blood  present.  Glycosuria  has 
been  noted  in  some  instances.  The  sediment  contains  hya- 
line, granular,  and  brown  granular  casts,  renal  epithelial 
cells,  and  more  or  less  blood. 

The  renal  disturbance  is  usually  an  active  hyperemia, 
which  may  be  quite  severe.  Rarely,  an  acute  nephritis 
with  marked  hematuria  develops,  especially  in  the  malig- 
nant types. 

In  certain  cases  there  is  sometimes  doubt  as  to  the 
diagnosis  between  typhoid  fever  and  an  acute  cerebrospinal 
meningitis.  Aside  from  a  bacteriologic  investigation,  an 
examination  of  the  urine  is  sometimes  of  assistance  in  arriv- 
ing at  a  conclusion.  The  principal  differences  in  the  urine 
in  the  two  diseases  are  as  follows  : 

Meningitis.  Typhoid  Fever. 

Fever  Urine  with  Exudation.  Fever  Ut'ine  without  Exudation. 

Color. — Normal  or  pale.  Color. — Very  high. 
Reaction.— Y2\xi'i\^  acid,   neutral,   or       Feactiojt.  —  Strongly  acid. 

alkaline. 
Chlorine. — Much    diminished  or  ab-       Chlorine. — Slightly  diminished. 

sent. 

Phosphates. — Much  increased.  Phosphates. — Diminished. 

MELANCHOLIA. 

In  this  disease  the  total  quantity  of  urine  is  usually  much 
diminished,  no  doubt  in  part  due  to  the  ingestion  of  very 
little  liquid.  The  specific  gravity  is  high,  and  the  coloring- 
matters  and  normal  solids  are  relatively  increased.  The 
urine  is  frequently  heavily  loaded  with  urates  and  oxalates. 
The  indoxyl  is  generally  increased.  The  irritating  action 
of  the  concentrated  urine,  and  in  some  instances  the 
mechanic  irritation  by  the  crystals  of  uric  acid  or  calcium 
oxalate,  may  be  the  cause  of  slight  albuminuria  and  a  renal 
congestion  (active  hyperemia). 

ACUTE  MYELITIS. 

Owing  to  an  involvement  of  the  sphincters  in  this  dis- 
ease retention  or  incontinence  of  urine  is  an  early  symptom. 
An  acute  or  chronic  cystitis  may  rapidly  develop,  when  the 


EPILEPSY.  395 

urine  becomes  faintly  acid  or  alkaline,  bloody,  and  purulent. 
In  such  cases  the  danger  of  a  pyelonephritis  by  extension 
is  very  great ;  not  infrequently,  death  occurs  during  uremic 
coma.  One  very  prominent  feature  of  the  urine  in  acute 
myelitis  is  a  marked  increase  in  the  indoxyl. 

EPILEPSY. 

Temporary  albuminuria  accompanied  by  more  or  less 
renal  disturbance  is  of  frequent  occurrence,  especially  in 
those  cases  of  epilepsy  in  which  the  convulsive  seizures 
succeed  each  other  very  rapidly.  Immediately  following 
the  attacks  the  quantity  of  urine  is  often  much  increased, 
the  color  pale,  the  specific  gravity  low,  and  the  reaction 
faintly  acid.  At  this  time  the  urea,  phosphates,  and  uric 
acid  are  said  to  be  increased. 

As  suggested  by  Taylor, ^  the  question  of  auto-intoxica- 
tion is  to  be  considered  as  a  possible  cause  of  albuminuria 
and  the  renal  disturbances  in  cases  of  severe  nervous 
affection.  It  is  quite  probable  that  the  nervous  disease 
itself  may  give  rise  to  certain  products  that  are  later  ex- 
creted by  the  kidneys.  This  is,  however,  contrary  to  the 
view,  as  generally  held,  that  the  effete  products  normally 
excreted  by  the  urine  are  sometimes  retained  in  the  body, 
and  that  they  are  the  direct  cause  of  various  nervous  dis- 
turbances. 

ACUTE  ARTICULAR  RHEUMATISM. 

In  acute  rheumatism  the  urine  has  the  characteristics  of 
that  of  an  acute  disease.  It  is  small  in  quantity,  has  a  high 
color,  and  a  high  specific  gravity — 1025  to  1030.  Rela- 
tively, the  quantity  of  urea  is  increased,  absohitely,  usually 
diminished.  The  uric  acid  is  often  both  relatively  and  abso- 
lutely increased,  sometimes  to  a  much  larger  extent  than  in 
most  of  the  other  acute  diseases.  The  urine,  upon  cooling, 
may  contain  an  abundant  deposit  of  amorphous  urates. 
The  chlorides  and  phosphates  are  only  moderately  dimin- 
ished in  an  uncomplicated  case  ;  the  sulphates  are  often  in- 
creased. If  a  pericarditis  develops,  the  chlorides  and  phos- 
phates become  very  much  diminished,  and  may  temporarily 
entirely  disappear  from   the  urine.      A  sudden   fall   in   the 

1  "Boston  Med.  and  Surg.  Journ.,"  Sept.  22,  1898. 


396  DISEASES  OUTSIDE  OF  THE  URINARY  TRACT. 

amounts  of  these  two  constituents  of  the  urine  is,  therefore, 
indicative  of  a  serious  complication. 

Albumin  is  usually  present,  but  in  very  small  amount — 
slightest  possible  trace.  Rarel)',  it  occurs  in  large  quantity 
attended  by  an  acute  nephritis,  of  which  the  urinary  sedi- 
ment bears  abundant  evidence.  In  the  average  case  of 
acute  rheumatism  the  sediment  contains  only  a  very  few 
renal  casts,  renal  cells,  and  an  occasional  blood  globule,  free 
and  adherent  to  casts  ;  in  other  words,  the  sediment  is  char- 
acteristic of  an  active  hyperemia. 

GOUT. 

During  an  attack  of  gout  the  volume  of  urine  is  gener- 
ally diminished,  the  color  is  high,  and  the  specific  gravity 
is  above  the  normal.  The  uric  acid  is  diminished  during 
the  paroxysm  ;  although  it  is  probably  formed  in  unusual 
quantities  in  this  disease,  the  deposit  of  urates  in  the  joints 
and  tissues  accounts  for  the  deficient  elimination  by  the 
kidneys.  Usually,  the  quantity  of  urea  is  not  materially 
altered  during  the  paroxysm  of  gout.  The  phosphates  are 
generally  much  diminished.  Albumin  is  nearly  always 
present,  but  usually  in  very  small  amount.  The  sediment 
contains  hyaline,  granular,  and  brown  granular  casts,  renal 
cells,  and  altered  blood  free  and  adherent  to  casts — the  evi- 
dences of  a  secondary  active  hyperemia  of  the  kidne}-. 

Between  the  attacks  or  paroxysms,  the  quantity  of  urine 
is  normal  or  even  increased.  The  normal  solids  are  usually 
about  normal,  except  the  uric  acid,  which  is  now  eliminated 
in  increased  amount ;  this  is  especially  marked  immediately 
following  the  paroxysm.  Evidence  of  a  more  or  less  marked 
renal  irritation  persists  between  the  attacks. 

It  should  be  borne  in  mind  that  in  chronic  gout  a  chronic 
interstitial  nephritis  is  not  uncommon.  Under  such  circum- 
stances the  quantity  of  urine  is  increased  ;  absolutely,  the 
urea  is  much  diminished,  albumin  is  present,  but  usually  in 
minute  quantity,  and  the  casts  in  the  sediment  are  generally 
of  the  small,  narrow,  hyaline,  and  finely  granular  order. 

Sugar  may  be  found  intermittently  in  the  urine  of  gouty 
person.s — gouty  glycosuria.  The  condition  may  pass  into 
true  diabetes,  but  it  is  usually  veiy  amenable  to  treatment. 
Oxaluria  may  also  be  present.  Calculi  are  not  uncom- 
mon in  gouty  subjects. 


ANEMIA.  397 

ANEMIA. 

In  the  various  forms  of  anemia  the  urine  presents  certain 
characteristics  that  are  common  to  all.  The  twenty-four- 
hour  quantity  is  generally  diminished — looo  c.c.  to  1200 
c.c.  ;  the  color  is  pale  ;  the  specific  gravity  is  below  the 
normal — about  1015  ;  and  the  reaction  is  acid.  Relatively 
and  absolutely  the  normal  solids  are  diminished,  but  the 
degree  of  diminution  is  dependent  largely  on  the  appetite 
and  general  metabolism. 

In  simple  anemia  and  chlorosis  the  urine  occasionally 
contains  the  slightest  possible  trace  of  albumin  and  formed 
renal  elements  in  the  sediment ;  on  the  other  hand,  albu- 
min and  renal  casts  may  be  absent. 

In  leukemia  the  presence  of  a  minute  trace  of  albumin 
and  renal  casts  is  perhaps  more  common  than  in  simple 
anemia.  Fatty  cells  and  fat  adherent  to  the  casts  are  not 
uncommon.  The  indoxyl  is  frequently  increased.  Abso- 
lutely, the  urea  is  diminished.  The  uric  acid  excreted  is 
always  in  excess,  and,  perhaps,  as  suggested  by  Salkowski, 
stands  in  direct  relation  to  the  splenic  tumor  or  to  the 
abundant  leucocytes.  The  proportion  of  uric  acid  to  urea 
may  be  as  high  as  i  to  15. 

In  pernicious  anemia  the  urine,  although  usually  pale, 
may  be  highly  colored  from  the  excess  of  so-called  patho- 
logic urobilin  (Hunter  and  Mott).  The  uric  acid  is  in- 
creased. Albumin,  var}dng  in  quantit)-  from  the  slightest 
possible  trace  to  a  trace,  is  usually  present  in  the  late  stages 
of  the  disease,  and  the  sediment  usually  contains  renal  casts, 
granular  renal  cells,  and  a  small  quantity  of  blood.  Von 
Jaksch  has  noted  the  presence  of  peptonuria  in  this  disease, 
but  so  far  as  known  it  has  little  or  no  significance. 

SCURVY. 

In  this  disease  the  quantity  of  urine  is  reduced,  the 
coloring-matters  are  increased,  and  the  urine  may  contain 
a  large  amount  of  blood  pigment — hemoglobinuria.  Abso- 
lutely, the  normal  solids  are  diminished,  especially  the 
chlorine.  The  urine  is  generally  albuminous,  and  some- 
times albumin  is  present  in  large  amount,  especially  if  there 
be  hemoglobinuria  or  an  acute  nephritis.  The  sediment 
usually  contains   renal  casts,   renal   cells,  and  in  case   of 


398  DISEASES  OUTSIDE  OF  THE  URINARY  TRACT. 

hemoglobinuria  an  abundance  of  brown  granular  matter. 
Hematuria  is  sometimes  present,  and  under  all  circum- 
stances should  be  distinguished  from  a  hemoglobinuria. 
The  author  has  occasionally  met  with  a  genuine  acute 
nephritis  in  this  disease.  A  more  or  less  marked  renal 
congestion  is  not  uncommon. 

CARBOLIC  AQD  POISONING. 

In  this  condition  the  urine  is  diminished  in  quantity ; 
the  color  is  variable,  being  usually  pale  or  normal  when 
freshly  voided,  but  upon  standing  exposed  to  the  air 
becomes  smoky  and  finally  very  dark  ;  occasionally,  the 
urine  is  dark  when  it  is  passed.  This  characteristic  change 
of  color,  following  the  external  or  internal  use  of  carbolic 
acid  and  other  phenol  compounds,  is  due  to  an  oxidation 
of  the  decomposition  products  of  the  phenol  or  phenol 
compounds.  (See  Color  of  the  Urine,  p.  25.)  The 
specific  gravity  is  usually  normal  or  diminished  ;  it  may  be 
above  the  normal.  The  reaction  is  acid.  Relatively,  the 
normal  solids  are  normal  or  diminished,  depending  upon 
the  severity,  and  occasionally  they  are  relatively  increased  ; 
absolutely,  diminished,  especially  the  ordinary  sulphates, 
while  the  conjugate  sulphates  are  much  increased.  (See 
Phenol-potassium  Sulphate,  p.  88.) 

The  urine  contains  albumin  ;  usually  a  very  slight  trace, 
but  in  the  severe  cases  it  may  be  as  high  as  ^^  of  i  per 
cent.  The  sediment  contains  hyaline,  granular,  and  brown 
granular,  and  sometimes  epithelial  casts,  renal  cells,  and 
abnormal  blood  free  and  adherent  to  the  casts.  A  more 
or  less  marked  renal  congestion  is  the  rule,  but  occasion- 
ally a  true  acute  nephritis  is  present. 

Care  should  be  taken  not  to  confound  a  dark  urine  fol- 
lowing the  use  of  phenol  compounds  with  a  urine  contain- 
ing melanin,  in  which  case  the  urine  is  often  pale  when 
passed,  but  upon  exposure  to  the  air  becomes  dark.  (See 
Melanin,  p.  190.) 

POISONING  BY  PHOSPHORUS  AND  ARSENIURETED 
HYDROGEN. 

The  characteristics  of  the  urine  in  cases  of  poisoning  by 
arseniureted  hydrogen  and  phosphorus  are,  for  the  most 
part,  identical.      Hemoglobinuria  is  the  principal  symptom. 


POISONING  BY  PHOSPHORUS.  399 

The  quantity  of  urine  is  diminished.  The  normal  sohds  are 
greatly  diminished,  especially  the  urea.  In  severe  cases 
leucin  and  tyrosin  may  appear  in  the  urine.  Albuminuria  is 
inv^ariably  present  ;  usually,  the  amount  of  albumin  is  large, 
although  the  quantity  will  depend  on  the  severity  of  the 
case.  The  sediment  will  contain  numerous  brown  granular 
and  fatty  casts,  fatty  and  brown  granular  renal  and  com- 
pound granule  cells,  a  variable  but  usually  small  amount  of 
blood,  and  sometimes  crystals  of  leucin  and  tyrosin — evi- 
dences of  extensive  fatty  degenerative  changes  in  the 
kidney  plus  a  hemoglobinuria. 


APPENDIX  A. 


METHOD  OF  RECORDING  URINARY  EXAMINA- 
TIONS. 

The  advisability  of  making  and  preserving  urinary  records 
is  obvious,  since  it  is  only  by  this  means  that  the  progress 
of  disturbances  or  diseases  of  the  kidney  (favorable  or  un- 
favorable) can  be  followed  from  week  to  week,  or  month  to 
month,  or  year  to  year.  Such  records  should  be  made  on 
separate  sheets  of  paper  provided  for  the  purpose  and  in- 
corporated with  the  clinical  history  and  physical  examina- 
tion of  the  patient,  or  be  kept  in  a  book  by  themselves  with 
cross-references  to  the  volume  containing  the  clinical  his- 
tory, etc.  For  ordinary  use  printed  urine  blanks  (see  p. 
401)  can  be  obtained,  and  as  each  test  is  made  the  result, 
indicated  by  abbreviations,  should  be  affixed  to  the  spaces 
left  for  the  purpose. 

The  abbreviations  used  upon  the  blank  forms  have  the 
following  meanings  :  UpJi.  =  urophaeine  ;  hid.  =  indoxyl ; 

67.  =  chlorine  ;  &.  =  urea  ;  W.  =^  uric  acid  ;  Sf.  =  sul- 
phates ;  E.  P.  ^^  earthy  phosphates  ;  A.  P.  =^  alkaline 
phosphates  ;  S/'.  Gr.  =  specific  gravity  ;  Sed.  =  sediment ; 
A/d.  =  albumin,  etc. 

The  common  abbreviations  used  in  recording  the  results 
of  analysis  are  :  -f  =  increased  ;  —  =  diminished  ;  n  = 
normal.  For  much  increased  or  much  diminished  :  m  + 
and  m  — ,  respectively  ;  similarly,  si.  -f  and  si.  —  for  a 
slight  increase  and  slight  decrease.  Other  abbreviations, 
according  to  the  habit  and  convenience  of  the  recorder, 
may  equally  well  be  adopted. 

The  plan  of  incorporating  the  urinary  records  into  book 
form  is  to  be  encouraged,  especially  for  those  who  make  a 
large  number  of  analyses.  Such  a  book  properly  indexed 
can  be  prepared  by  any  competent  printer  at  a  moderate 
cost.  A  record  of  this  kind  is  far  more  serviceable  and 
convenient  than  the  separate  sheets. 

400 


RECORD  OF  URINARY  EXAMINATIONS.  401 


ANALYSIS   OF   URINE. 


Date 

Name j 

Amt.  in  t7oenty-four  hours  ^=^  Sp.   Gr. 

Color  =.  Sed.  = 

Odor  = 
Reaction  = 


uph.  =  cr.  (fc)=        a.  =  E.  p. 


Ind.  =  C/.=  Sf.=  A.  F. 

Albumin  = 
Bile  Pigments  = 
Sugar = 
Sediment  = 


C  C/.  :=  grams.     P^0^=  grams. 

Quant.   - 

(  CI.  =  "         Sugar  =  " 


Diagnosis  = 
26 


402  URINARY  EXAMINATIONS. 

Tabular  Arrangement  of  Heller's  Tests  (modified). 

Physical  Properties. 

Color. — Pale,  normal,  high,  or  dark. 

Odor. — 

Reaction. — Acid,  neutral,  or  alkaline. 

Sp.  Gr. — By  urinometer. 

Sediment. — Slight,  considerable,  or  much. 

Normal  Constituents. 

IjROPHiEiNE  (Uph.). — 7  c.c.  HjjSO^  -\-  double  quantity  of  Ur. 
=  immediate  garnet-red  color. 

INDOXYL  (Ind.).  — 15  c.c.  HCl  (-\-  2  gtt.  HNO3)  +  30  gtt. 
Ur.  =:  amethyst  color,  developing  in  from  five  to  twenty 
minutes. 

Urea  (U.).— With  NaOBr.      (Squibb's  apparatus.) 
Uric  Acid  (\J.).—}4  tt.  Ur.  +  HCl  =  U  cryst.  in  24°. 

Chlorine  (CI.).— Ur.  +  HNO,  +  AgNO,  (1:8)  =  soHd 
ball  of  AgCl,  if  normal. 

Sulphates  (Sf.).— i^  tt.  Ur.  +  BaCl^  sol.  (1:4  sol.  +  HCl) 
=  ppt.  j/2  concav.  of  tt.  in  from  eighteen  to  twenty- 
four  hours,  if  normal. 

Earthy  Phosphates  (E.  P.). — }4  tt.  Ur.  +  NHpH  =  ppt. 
j(  to  yz  in.  in  tt.,  in  from  eighteen  to  twenty-four  hours, 
if  normal. 

Alkaline  Phosphates  (A.  P.). — Filtrate  from  E.  P.  -\-  MgSO^ 
sol.  (MgSO,  +  NH^Cl  +  NH^H)  =  ppt.  }4  to  }{  in. 
in  tt.,  in  from  eighteen  to  twenty-four  hours,  if  normal. 

Abnormal  Constituents. 

Albumin  (Alb.). — Heat  or  HNO3  =  coagulum  or  zone. 

Bile  Pigments. — Marechalt's  test  (iodine). 

Sugar. — Fehling's  solution.  Phenylhydrazin  test.  Fermenta- 
tion test. 

Sediment. — Let  settle  or  centrifugalize,  and  examine  by  micro- 
scope. 


ORDER  OF  APPLYING  TESTS.  403 


ORDER  OF  APPLYING  TESTS. 

In  the  routine  analysis  of  a  urine  it  is  advisable  first  to 
note  the  twenty-four-hour  quantity,  the  color,  the  odor  if 
at  all  peculiar,  the  reaction,  and  the  specific  gravity.  The 
next  in  order  should  be  the  tests  for  urophaeine  and  indoxyl, 
and  then  the  test  for  albumin.  If  more  than  a  trace  of 
albumin  be  present,  it  must  be  removed  before  testing  for 
chlorides,  sulphates,  or  sugar.  Having  removed  the  albu- 
min by  heat  from  one-third  or  one-half  of  a  test-tube  of  the 
urine  after  the  addition  of  one  drop  of  acetic  acid  (see  p. 
129)  the  test  for  chlorides,  sulphates,  and  sugar  should 
then  be  performed.  If  in  the  test  for  albumin  a  zone  of 
acid  urates  appears,  it  should  be  noted.  Such  a  zone 
indicates  a  relative  excess  of  uric  acid  and  urates.  The 
tests  for  earthy  and  alkaline  phosphates  are  next  in  order, 
and  then  the  test  for  bile  pigments. 

The  quantitative  test  for  urea  should  be  performed  in 
every  instance,  and  this  is  most  conveniently  done  by 
means  of  the  Squibb  or  the  Doremus  apparatus.  The  per- 
centage should  be  noted,  and  the  total  number  of  grams  of 
urea  calculated.  If  sugar  be  present,  it  should  also  always 
be  quantitated,  and  the  total  quantity  reported  in  grams. 

The  amount  of  sediment  that  a  urine  contains  can  only 
be  determined  after  the  urine  has  completely  settled.  The 
degree  of  opacity  of  the  urine  can  not  always  be  considered 
acriterion  of  the  amount  of  sediment  present.  A  urine  may 
be  very  turbid,  for  example,  by  bacteria,  and  yet  contain 
very  little  sediment.  As  soon  as  the  sediment  has  com- 
pletely settled,  it  should  be  carefully  examined  by  means 
of  the  microscope  for  casts,  renal  cells,  fatty  cells,  fat  adher- 
rent  to  the  casts,  blood,  pus,  crystalline  elements,  etc. 

METHOD  OF   MAKING  DIAGNOSES  OF  DISEASES  OF  THE 
KIDNEYS  FROM  THE  URINE. 

The  diagnoses  of  the  different  diseases  of  the  kidneys 
are  made  chiefly  by  exclusion. 

It  has  been  shown  that,  even  in  a  single  affection  of  the 
kidneys,  the  characteristics  of  the  urine  vary  with  the  severity 
of  the  process  and  the  extent  of  the  diseased  condition  : 
furthermore,  that  diseases  of  the  kidneys  are  very  liable  to 
become  complicated  by  other  pathologic  conditions  of  these 


404  APPENDIX  A. 

organs.  Thus,  the  urine  becomes  modified  to  a  greater  or 
less  extent  from  what  one  would  find  if  the  original  disease 
were  uncompHcated.  For  example,  a  subacute  or  chronic 
disease  of  the  kidneys  is  very  liable  to  be  complicated  by  a 
more  or  less  severe  acute  process ;  under  such  circum- 
stances, the  underlying  subacute  or  chronic  process  may  be 
partially  or  entirely  obscured  by  the  acute  complication. 
Obviously^  an  absolute  standard  of  disease,  to  which  an  un- 
k)ioiun  specimen  of  urine  should  conform,  is  entirely  out  of  the 
question.  In  other  words,  a  urinary  disease  is  not  invariably 
accompanied  by  a  urine  of  specific  character,  but  by  charac- 
teristics subject  to  more  or  less  variation. 

In  the  foregoing  pages  of  this  work  the  author  has 
endeavored  to  outline  a  fairly  typical  urine  of  each  disease. 
Having  made  an  accurate  examination  of  an  unknown  speci- 
men of  urine,  it  will  be  found  that  the  characteristics  of  such 
a  urine  harmonize  in  a  general  way  with  those  known  to  be 
associated  with  this  or  that  disease. 

In  the  consideration  of  a  given  urine  that  shows  evidence 
of  a  renal  disturbance  or  disease  (presence  of  renal  casts) 
the  first  and  most  important  feature  from  the  standpoint  of 
diagnosis  is  the  total  quantity  of  urine. 

A  diminished  quantity  (less  than  1500  c.c.)  is,  as  a  rule, 
indicative  of  any  of  the  following  conditions  : 

1.  Active  hyperemia. 

2.  Passive  hyperemia. 

3.  Acute  nephritis  (first  and  second  stages). 

4.  Subacute  glomerular  nephritis  (all  stages). 

5.  Chronic  renal  diseases  toward  death. 

An  increased  quantity  (more  than  1500  c.c.)  is  strongly 
suggestive  of  any  of  the  following  conditions  : 

{a)     Convalescence  from  severe  active  hyperemia. 

{p)    Convalescence  from  acute  nephritis. 

ic)    Chronic  interstitial  nephritis. 

{d^  Chronic  diffuse  nephritis. 

(r)     Amyloid  infiltration. 

Having  limited  the  probable  renal  disturbance  or  disease 
to  the  class  characterized  by  a  small  or  a  large  quantity  of 
urine,  the  next  step  is  to  distinguish  between  the  different 
renal  conditions  of  that  class  by  means  of  the  quantities  of 
normal  solids,  the  amount  of  albumin,  and  the  peculiarities 
of  the  sediment — /.  e.,  the  presence  or  absence  of  blood  on 
casts,  the  presence  or  absence  of  fat  from  the  kidney,  the 


METHOD  OF  MAKING  DIAGNOSES.  405 

size  and  character  of  the  renal  casts,  etc.  In  this  way  the 
most  probable  disturbance  or  disease  of  the  kidneys  can 
usually  be  narrowed  down  to  one  or,  perhaps,  two  of  the 
conditions  under  consideration. 

Having  arrived  at  the  most  probable  renal  affection,  the 
next  step  is  to  determine  the  location  and  nature  of  any 
complications  that  may  be  present,  whether  in  the  kidneys 
or  in  some  other  portion  of  the  urinary  tract. 

In  the  application  of  this  plan  of  urinary  diagnosis  it  is 
obvious  that  the  student  must  thoroughly  familiarize  him- 
self with  the  characteristics  of  the  urine  of  each  disease  of 
the  kidneys,  as  well  as  of  those  of  other  portions  of  the 
urinary  tract. 


APPENDIX   B. 


REAGENTS  AND  APPARATUS    FOR  QUALI= 

TATIVE  AND  QUANTITATIVE 

ANALYSIS  OF  URINE. 

The  reagent  bottles  should  be  made  of  pure,  clear  glass, 
free  from  lead  and  other  impurities.  Those  for  liquid 
reagents  should  have  a  capacity  of  about  250  c.c,  while 
those  for  solid  reagents  need  not  have  a  capacity  over 
120  c.c.  All  bottles  should  be  fitted  with  ground-glass 
stoppers,  and  should  have  labels  upon  them  in  raised  glass 
letters,  or  a  ground-glass  label  with  black  letters,  and  the 
chemic  symbol  of  the  reagent  below  and  separate  from  the 
lettering. 

Many  of  the  reagents  given  below  are  not  really  neces- 
sary for  the  ordinary  routine  analysis  of  urine,  but  for 
efficient  laboratory  work  all  of  those  given  will  be  found 
necessary. 

LIQUID  REAGENTS. 

Sulphuric    acid,    C.    P.  (H^-      Tinct.  iodine,  U.  S.  P. 


SOJ. 
Hydrochloric    acid,     C.     P. 

(HCl). 
Nitric  acid,  C.  P.  (HNO3). 
Acetic  acid  (HQHgO,). 
Amnionic      hydrate     (NH^- 

OH). 
Sodic  hydrate   (NaOH),  U. 

S.  P. 
Magnesia  mixture.      (See  p. 

108.) 
Sol.  potassium  ferrocyanide 

(I  :  10). 


Sol.  lead  acetate  (i  :  5). 
Sol.  basic  lead  acetate  (i  :  5). 
Alcohol,  95  per  cent. 
Sodic  hydrate  for  urea.   (See 

P-  52.) 
Bromine  (modified)  for  urea. 

(See  p.  53.)  _ 
Fehling's  solution.     (Seep. 

H7-) 

A.  Cupric  sulphate  so- 
lution. 

B.  Alkaline  tartrate  so- 
lution. 


406 


REAGENTS. 


407 


Sol.  barium  chloride.      (See 

p.   112.) 
Sol.  ferric  chloride — aqueous 

(I  :  lo). 
Millon's    reagent.       (See  p. 

i68.) 
Esbach's   reagent,     (See    p. 

131-) 
Sol.  silver  nitrate  (i  :  8). 


Phenylhydrazin  (pure). 

Chloroform. 

Formaline. 

Sol.  boric  acid  (saturated). 

Standard  sol.  silver  nitrate. 
(See  p.  102.) 

Standard  sol.  uranium  ni- 
trate.    (See  p.  109.) 

Distilled  water. 


SOLID  REAGENTS. 

[AH  reagents  should  be  chemically  pure. 


Cupric  sulphate. 
Caustic  soda. 
Sodium  chloride. 
Potassium  iodide. 
Potassium  chromate. 
Ammonium  sulphate. 
Magnesium  sulphate. 
Ammonium  chloride. 
Sodium  acetate. 
Potassium  ferrocyanide. 


Potassium  chlorate. 
Picric  acid. 
Citric  acid. 
Lead  acetate. 
Sulphanilic  acid. 
Sodium  nitrite. 
Sodium  carbonate. 
Mercuric  chloride. 
Potassium  bromide. 
Sodium  nitroprusside. 


APPARATUS. 

Test-tubes. 

Test-tube  brush. 

Test-tube  rack. 

Bunsen  burner  with  two  feet  rubber  tubing,  or  a  spirit  lamp. 

Urinometer  (Squibb  or  other  of  reliable  make). 

Urinometer  glass  with  foot  and  parallel  sides.     (See  Fig.  2.) 

Wine-glasses.     (See  Fig.  13.) 

Urea  apparatus  (preferably  Squibb' s). 

Urine  glasses.     (See  Fig,  24.) 

Funnels,  large  and  small. 

Filter  papers  (cut)  4,  6,  and  8  inches  in  diameter. 

Glass  tubing  for  pipettes. 

Glass  rods  (assorted  sizes). 

Litmus  paper  (red  and  blue). 

Graduates  (100,  500,  and  looo  c.c). 

Evaporating  dishes  (assorted  sizes  up  to  one  liter). 

Crucibles. 

Porcelain  spatula. 


408  APPENDIX  B. 

Platinum  wire  inserted  in  glass  rod. 

Platinum  foil. 

Burettes  (50  c.c,  graduated  in  tenths  of  a  cubic  centimeter). 

Retort  stand  with  burette  clamp  attached. 

Tripod  with  copper-wire  gauze  to  cover. 

Triangles. 

Water-bath  (preferably  copper  with  rings). 

Crucible  tongs. 

Beakers  (nests  of  six). 

Wash  bottle  (500  c.c). 

Flask  (250  c.c). 

Liter  flask  (graduated  on  neck). 

Graduated  pipettes  (5,  10,  and  50  c.c). 

Dropping  bottle,  bulb  stopper. 

Esbach's  albuminometer. 

Accurate  thermometer. 

Accurate  balances,  turning  at  i  milligram. 

Microscope — Zeiss,  Leitz,  or  Bausch  and  Lomb,  with  nose- 
piece  ;  objectives  corresponding  to  3,  5,  and  7  of  Leitz 
make,  and  i  and  3  eye-pieces,  Leitz  make  ;  Abbey  con- 
denser ;  and  -^  oil  immersion  lens. 

Glass  slides,  cover-glasses,  cedar  oil,  and  Canada  balsam 
(in  solution). 

Centrifuge  capable  of  2000  revolutions  per  minute. 


Plate  io 


10       20       30       iO       50       CO       70       SO       90 


r 


100  no    120  ISO    11,0  Vto   leo    170 

MnhiiilnPM 


Spectra  (after  Neubauer  and  Vogel). 

1.  (!,  Oxyhemoglobin  ;  3,  hemoglobin,  free  from  oxygen. 

2.  Methemoglobin  :  a,  in  neutral  solution  ;  l>,  in  alkaline  solution. 

3.  a,  Hematin  in  acid  alcoholic  solution  ;  5,  in  ammoniacal  solution  ;  c, 
reduced  hematin. 

4.  a,  Urobilin  in  acid  solution  ;  /',  zinc  salt  in  ammoniacal  solution. 


Spectra,  Continued  (after  Neurauer  and  Vogel). 

5.  Hematoporphyrin :    a,  acid ;    l>,  alkaline ;    r,    neutral ;    d,    metallic 
spectra. 

6.  Bilicyanin  :  a,  in  acid  solution  ;  b,  in  alkaline  solution. 

7.  Uroerythrin. 


Plate  i i 


30  iO  50  RO 


110  no 


F 

130 


no 


GC0.50    iO     30     -i'O      10      600      5S9      80        TO        60         50  Ifi  30  20 

C  J^  ^  '^ 

656.3  S89.3  527         oU.S 


493  SO 

F 

i86 


NDEX 


Abnormal  blood,  231 

constituents  of  the  urine,  1 17 
Abscess  of  the  kidney,  326 

of  the  prostate,  353 
Absolute  solids,  37 
Acetone  in  the  urine,  171 

clinical  significance  of,  171 
detection  of,  172 
Legal' s  test  for,  172 
quantitative  estimation  of,  172 
Acetonuria,  17 1 
Acid,  carbonic,  1 1 5 

conjugate  sulphuric,  1 14 

damaluric,  30 

damolic,  30 

fatty,  97 

fermentation,  32 

hippuric,  80 

lactic,  97 

nucleic,  75 

oxalic,  96 

phenylic,  30 

phosphoric,  determination  of,  109 

sarcolactic,  97 

succinic,  97 

sulphuric,  ill 

taurylic,  30 
Acidity,  causes  of  diminished,  ^^^ 

of  increased,  34 
Acids,  biliary,  178 
Active  hyperemia,  282 

severe,  286 
Acute  articular  rheumatism,  urine  in, 

.395 
diffuse  nephritis,  292 
general  peritonitis,  urine  in,  391 
myelitis,  urine  in,  394 
yellow  atrophy  of  the  liver,  urine 
in,  392 
Albumin  in  the  urine,  1 18 

approximate  estimation  of,  123 

detection  of,  122 

quantitative  estimation  of,    130, 

132 
removal  of,  129 
testing  for,  method  of,  122 
Albuminometer,  Esbach's,  131 


Albuminuria,  causes  of,  119 

clinical  importance  of,  1 19 

false,  121 

functional  or  physiologic,  1 20 

of  adolescence,  121 
Albumoses,  134 

clinical  significance  of,  135 

detection  of,  136 
Albumosuria,  135 
Alcapton,  28 

as  a  reducing  agent,  150 
Alkaline  carbonates,  29,  32 

phosphates,  107 
detection  of,  108 

tide,  32 
Alkalinity  of  the  urine,  32 
Allantoin,  76 

detection  of,  77 
Almen's  tannin  solution,  142 
Ammoniacal    decomposition    of   the 

urine,  S3 
Ammonio-magnesium  phosphate,  215 
Ammonium  urate,  211 
Amorphous  urates,  212 

treatment   of   sediment    contain- 
ing, 212 
Amphoteric  reaction,  ^3 
Amyloid  concretions,  260 

infiltration,  317 
Analysis  of  calculi,  280 
Anemia,  urine  in,  397 
Antialbumose,  134 
Antipeptone,  137 
Anuria,  25 

Apparatus  for  analysis  of  urine,  406 
Appendix,  400 
Aromatic  oxyacids,  82 

substances  in  the  urine,  80 
Arsenic  in  the  urine,  184 

test  for,  185 
Ascarides  in  the  urine,  269 


Bacteria  in  the  urine,  263 

cause  of  turbidity,  30 
Bacterial  casts,  256 
Barfoed's  reagent,  165 


409 


410 


INDEX. 


Barium  chloride,  standard  solution  of, 

"3 

solution  for  sulphates,  1 1 2 
Bausch  &  Lomb  hand  centrifuge,  203 
Bile  in  the  urine,  175 
Biliary  acids,  178 

clinical  significance  of,  179 
detection  of,  180 
isolation  of,  179 
quantitative  estimation  of,  181 
pigments,  175 

clinical  significance  of,  176 
detection  of,  177 
Bilirubin-calcium,  176 
Bilirubin  in  the  urine,  224 
Biuret  reaction,  139 
Black  urine,  28 
Bladder,  cancer  of,  348 
epithelium  from,  245 
inflammation  of,  342 
tuberculosis  of,  346 
tumors  of,  348 
Blood,  abnormal,  231 
in  the  urine,  230 

treatment  of  sediment  containing, 
231 
normal,  230 
Blood-casts,  254 
Blood-pigment,  Teichmann's  test  for, 

235 
Bloody  color  of  the  urine,  28 
Blue  color  of  the  urine,  28 
Boric  acid  as  a  preservative,  23 
Bowman,  theory  of,  17 
Bromides  in  the  urine,  187 


Cadaverin,  222 
Calcium  carbonate  calculi,  278 
oxalate,  96,  217 
calculi,  277 

clinical  significance  of,  220 
crystals  of,  218 
phosphate,  215 
urate,  212 
Calculi,  urinary,  270 

chemic  examination  of,  280 
constituents  of,  272 
Calculous  pyelitis,  335 
Calculus,  vesical,  344 
Cancer  of  the  bladder,  348 
of  the  kidney,  328 
of  the  prostate,  357 
Cane-sugar  in  the  urine,  170 
Carbohydrates  in  the  urine,  145 
Carbolic-acid  poisoning,  urine  in,  ^c 
Carbonates  in  the  urine,  115 

alkaline,  29 
Casts,  bacterial,  256 


Casts,  bacterial,  classification  of,  248 
crystalline,  256 
epithelial,  253 
false,  257 
fatty,  255 
fibrinous,  250 
granular,  252 
hyaline,  248 
renal,  247 
waxy,  251 
Cells,  compound  granule,  246 

seminal,  245 
Centrifugal   method  of  estimating  al- 
bumin, 132 
chlorides,  105 
phosphates,  iii 
uric  acid,  70 
of  obtaining  sediment,  200 
Centrifuges,  202,  203 
Cerebrospinal   meningitis,    urine    in, 

393 
Chloral  in  the  urine,  186 
Chlorides,  99 

clinical  significance  of,  lOO 

detection  of,  loi 

quantitative  estimation  of,  loi 
Chlorinated  lime,  solution  of,  52 
Cholera,  urine  in,  387 
Cholesterin  in  the  urine,  22S 

detection  of,  229 
Chronic  diffuse  nephritis,  314 

interstitial  nephritis,  305 
Chyle  in  the  urine,  30,  360 
Chyluria,  360 

Collection  of  urine  for  analysis,  22 
Coloring-matters,  90 
Color  of  the  urine,  25 

under  normal  conditions,  25 
under  pathologic  conditions,  26 
Compound  granule  cells,  246 
Concretions,  270 

amyloid,  260 

calcium  carbonate,  278 
oxalate,  277 

cystin,  278 

fibrin  and  blood,  280 

indigo,  279 

phosphatic,  277 

prostatic,  280 

uric  acid  and  urates,  276 

urostealith,  279 

xanthin,  278 
Constituents  of  normal  urine,  21 

of  lu'inary  calculi,  272 
Convalescence  from   acute   nephritis, 
296 

from  severe  active  hyperemia,  287 
Corpora  amylacere,  259 
Cover-glasses,  206 


INDEX. 


411 


Crystalline  casts,  256 
Cyclic  albuminuria,  121 
Cystic  disease  of  the  kidney,  329 
Cystin,  31,  221 

calculi,  278 

detection  of,  223 
Cystinuria,  causes  of,  222 

clinical  significance  of,  223 
Cystitis,  acute,  342 

chronic,  344 


Dark  color  of  the  urine,  27 
Day-  and  night-urine,  23 

collection  of,  23 
Deutero-albumose,  135 
Dextrose  in  urine,  145.     See  Glucose. 
Diabetes  mellitus,  368 

insipidus,  375 

phosphatic,  108 
Diabetic  coma,  373 
Diacetic  acid  in  the  urine,  1 74 

clinical  significance  of,  174 
detection  of,  175 
Diaceturia,  174 
Diagnosis  of  kidney  disease  from  the 

urine,  403 
Diamines  in  the  urine,  222 
Diazo  reaction,  Ehrlich's,  182 
Diffuse  nephritis,  acute,  292 

chronic,  314 
Diminished  acidity,  causes  of,  T^'i, 

quantity  of  urine,  causes  of,  24 
Diphtheria,  urine  in,  390 
Distoma  hematobium,  267 
Donne's  test  for  pus,  239 
Dysalbumose,  135 


Earthy  phosphates,  106 

cause  of  turbid  urine,  29 

detection  of,  108 

quantitative  estimation  of,  IIO 

Echinococci,  268 

Ehrlich's  diazo  reaction,  182 

Einhom's  saccharimeter,  160 

Electric  centrifuge,  202 

Epilepsy,  urine  in,  395 

Epithelial  casts,  253 

Epithelium  in  urine,  241 

Erysipelas,  urine  in,  386 

Esbach's  albuminometer,  131 

method    of    quantitating    albumin, 

131 

Ethereal  sulphates.  83,  114 

formation  of,  83 
Eustrongylus  gigas,  269 
Extraneous  substances  in  urine,  261 


False  albuminuria,  121 

casts,  257 
Fatty  acids  in  urine,  97 

casts,  255 
Febrile  acetonuria,  171 
Fehling's  solution,  147 

test  for  sugar,  147,  155 
Fermentation,  acid,  32 

-test  for  sugar,  152,  159 
Ferments  in  the  urine,  97 
Fever  urine,  378 
Fibrin  in  the  urine,  143 

clinical  significance  of,  143 
detection  of,  143 
Fibrinous  casts,   250 
Filaria  sanguinis  hominis,  267,  360 
Florence    reaction   for   seminal   fluid, 

259 
Fokker-Salkowski  method  for  estimat- 
ing uric  acid,  58 
Folin's    method    for    estimating   uric 

acid,  70 
Formalin  as  a  preservative,  23 
Fowler's    hypochlorite    method    for 

urea,  58 
Frohn's  reagent,  153 
Functional  albuminuria,    120 
Functions  of  the  kidneys,    17 
Furfurol  reaction  for  bile  acids,  181 
for  tyrosin,  227 


Gases  in  the  urine,  364 

General  diseases,  urine  in,  379 

Globulin  in  the  urine,  132 

clinical  significance  of,  133 
quantitative  estimation  of,  133 

Globuloses,  1 34 

Glomerular  nephritis,  subacute,  300 

Glucose  in  the  urine,  145 
bismuth  test  for,  153 
detection  of,  146 
Fehling's  test  for,  147 
fermentation  test  for,  152 
isolation  of,  146 
methylene-blue  test  for,  154 
Nylander's  test  for,  154 
phenylhydrazin  test  for,  150 
quantitative  detennination  of,  155 
Trommer's  test  for,  147 

Glycosuria,  368 

permanent,     368.     See      Diabetes 

Mellitus. 
temporary,  368 
traumatic,  369 

Glycuronic  acid  in  the  urine,  169 

isolation  and  detection  of,  170 

Gmelin's  test  for  bile  pigment,  177 

Gonococci,  266 


412 


INDEX. 


Gonorrhea,  358 

Gout,  urine  in,  396 

Gram' s  method  of  staining  gonococci, 

266 
Granular  casts,  252 
Grape-sugar  in  the  urine,  145.     See 

Glucose. 
Greenish  tint  to  the  urine,  28 
Guanin  in  the  urine,  71 


Halliburton's  table  of  colors,  28 
Hand  centrifuge,  203 
Heat-test  for  albumin,  125 
Heidenhain,  experiments  of,  18 
Heintze's  method  of  estimating  uric 

acid,  66 
Hematogenous  icterus,  178 
Hematoidin  in  the  urine,  224 
Hematoporphyrin  in  the  urine,  187 
clinical  significance  of,  189 
detection  of,  190 
separation  of,  189 
spectra  of,  188 
Hematuria,  232 

clinical  significance  of,  232 
Hemialbumose,  134 
Hemin  crystals,  236 
Hemipeptone,  137 
Hemoglobin  in  the  urine,  142 
oxy-,  142 
reduced,  142 
Hemoglobinuria,  362 
Hepatogenous  icterus,  1 78 
Heteroalbumose,  134 
Heteroxanthin,  73 

detection  of,  74 
High  color  of  the  urine,  25,  26 
Hippuric  acid,  80 
detection  of,  81 
quantitative  estimation  of,  82 
Hoffman's  test  for  tyrosin,  226 
Hopkin's  method  of  estimating  uric 

acid,  67 
Hoppe-Seyler,  classification  of,  21 
Hyaline  casts,  248 
Hydatid  cysts  of  the  kidney,  268 
Hydrochinone  in  the  urine,  27 
Hydrogen  peroxide  in  the  urine,  1 16 
Hydronephrosis,  337 

symptoms  of,  338 

urine  in,  338 
Hydrooaracumaric  acid  in  the  urine, 

82 
Hydruria,  25 
Hyperemia,  active,  282 

passive,  289 

severe  active,  286 


Hypobromite  method  of  quantitating 

urea,  50 
Hypochlorite  method  of  quantitating 

urea,  50 
Hypoxanthin,  74 

detection  of,  75 
Hysteria,  urine  in,  393 


Icterus,  hematogenous,  176,  178 

hepatogenous,  176,  178 
Increased  acidity  of  urine,  causes  of,  34 

quantity  of  urine,  causes  of,  24 
Indigo-blue,  84 
Indigo  calculi,  279 
Indigo-red,  84 
Indoxyl -potassium  sulphate,  84 

clinical  significance  of,  85 

detection  of,  86 
Infiltration,  amyloid,  317 
Inorganic  constituents  of  the  urine,  99 
Inosite  in  urine,  167 

detection  of,  168 

isolation  of,  168 
Interstitial  nephritis,  chronic,  305 

senile,  313 
Intestinal  obstruction,  urine  in,  391 
Iodides  in  the  urine,  187 
Iodoform  test  for  acetone,  172.     See 

Licbeu^ s  Test. 
Iron  in  the  urine,  116 

detection  of,  116 


Jaffe's  urobilin,  90 

Jaundice,  176,  178.     See  Icterus. 


Kidney,  abscess  of,  326 

cystic  disease  of,  329 

disturbances  and  diseases  of,  282 

tuberculosis  of,  321 

tumors  of,  328 
Kidneys,  functions  of,  17 
Kreatin,  77 
Kreatinin,  77 

detection  of,  79 
Kreatinin-zinc  chloride,  78 


Lactic  acid  in  the  urine,  97 
Lactose  in  the  urine,  164 

detection  of,  165 

isolation  of,  164 
Laiose  in  the  urine,  166 

detection  of,  167 
Lead  in  the  urine,  184 

test  for,  185 
Legal' s  test  for  acetone,  172 


INDEX. 


413 


Leo's  sugar,  i66.     See  Laiose. 
Leucin,  224 

detection  of,  225 
Sherer's  test  for,  225 
Leucocytes  in  the  urine,  236 
Leucomaines  in  the  urine,  196 
Levulose  in  the  urine,  165 

detection  of,  166 
Lieben's  test  for  acetone,  172 
Liebig'  s  method  of  estimating  urea,  47 
Lipaciduria,  97 
Liver,  acute  yellow  atrophy  of,  urine 

in,  392 
Local  caseating  tuberculosis,  321 
Loetfler's    methylene-blue     solution, 

266 
Ludwig,  theory  of,  18 


Magnesia  mixture,  108 
Malarial  fever,  urine  in,  385 
Marechalt's  test  for  bile  pigments,  177 
Melancholia,  urine  in,  394 
Melanin  in  the  urine,  26,  190 

clinical  significance  of,  191 

detection  of,  191 
Melanogen,  190 
Meningitis,    cerebrospinal,   urine   in, 

Mercuric  nitrate,  standard  solution  of, 

48 
Mercury  in  the  urine,  186 

test  for,  186 
Methemoglobin,  27 
Method  of  taking  specific  gravity,  37 

of  testing  for  albumin,  122 
Micrococcus  ureee,  264 
Micro-organisms  in  the  urine,  263 
Microscopes,  206 
Microscopic   examination    of   urinary 

sediments,  206 
Miliary  tuberculosis,  acute,  321 
Milk  sugar  in  the  urine,  164 
Millon's  reaction  for  proteids,  117 

reagent,  168 
Mohr's  method  of  estimating  chlorine, 

lOI 

Mounting  of  urinary  sediments,  202 
Mucin  in  the  urine,  98,  140 
Murexide  test  for  uric  acid,  66 
Myelitis,  acute,  urine  in,  394 


Neisser,  gonococcus  of,  266,  358 
Nephritis,  acute  diffuse,  292 
chronic  diffuse,  314 

interstitial,  305 
interstitial,  305 
senile,  300 


Nephritis,  subacute  glomerular,  300 
Neubauer-Salkowski  method  of   esti- 
mating chlorine,  103 
Nitric  acid  test  for  albumin,  122 
Nomenclature,  19 
Nonorganized  sediments,  208 
Nonpathogenic  bacteria  in  the  urine, 

263 
Normal  blood,  230 

urine,  constituents  of,  2 1 

quantitative  composition  of,  21 
urobilin,  90 
Nucleic  acid,  75 

detection  of,  76 
Nucleo-albumin,  I40 

clinical  significance  of,  141 
detection  of,  141 
Nylander's  test  for  sugar,  154 

Obstruction,    intestinal,   urine    in, 

391 
Obstructive  suppression,  25 

Odor  of  the  urine,  30 

Oliguria,  25  .      ,       .     , 

Order    of    application    of    chemical 

tests,  403 
Organic  constituents  of  normal  urine, 

41 
Organized  sediments,  230 
Origin  of  urobilin,  90 
Oxalate  of  calcium,  96,  217 

crystals  of,  218 
Oxalic  acid  in  the  urine,  96 
Oxyacids,  aromatic,  82 
Oxybutyric  acid,  A-,  in  the  urine,  160 
Oxyhemoglobin,  142 

Paraoxyphenyl-acetic  acid  in  the 

urine,  82 
Parasites,  267 
Paraxanthin,  75 

detection  of,  75 
Parkes'  table  of  urinary  constituents, 

21 
Passive  hyperemia,  289 
of  pregnancy,  290 
Pathogenic  bacteria  in  the  urine,  265 
Pathologic  urobilin,  90 
Peculiar  odor  of  the  urine,  31 
Pelvic  epithelium,  243 
Penicillium  glaucum,  265 
Pepsin  in  the  urine,  97 
Peptone,  136 

clinical  significance  of,  137 

detection  of,  138 

separation  of,  1 38 
Peritonitis,  urine  in,  391 


414 


INDEX. 


Permanent  glycosuria,  368.    See  Dia- 
betes Mellitus. 
Pettenkofer's  test  for  bile  acids,  180 
Phenol -potassium  sulphate,  88 
clinical  significance  of,  88 
detection  of,  89 
determination  of,  89 
Phenylglucosazone,  151 
Phenylhydrazine  test  for  sugar,  1 50 
Phosphates,  106,  214 

alkaline,  107 

clinical  significance  of,  107,  216 

earthy,  106 

quantitative  determination  of,  109 

separate   estimation  of  earthy  and 
alkaline,  no 
Phosphatic  diabetes,  108 
Phosphaturia,  107 
Phosphorus-poisoning,  urine  in,  398 
Physical  properties  of  the  urine,  24 
Physiologic  albuminuria,  120 
Pigments,  biliary,  175 
Piotrowski's  reaction  for  proteids,  1 17 
Pipette  for  sediments,  205 
Piria's  test  for  tyrosin,  227 
Pneumaturia,  364 
Pneumonia,  urine  in,  383 
Polariscope,  estimation  of  sugar  by, 

160 
Polyuria,  25 

Potassium  ferrocyanide  test  for  albu- 
min, 126 

permanganate,  standard  solution  of, 
68 

urate,  212 
Preservation  of  urinary  sediments,  261 
Preservatives  for  urine,  23 
Prostate,  abscess  of,  353 

cancer  of,  357 
Prostatic  epithelium,  245 

plugs,  257 
Prostatitis,  acute,  351 

chronic,  353 

tubercular,  356 
Protalbumose,  134 
Proteids  in  the  urine,  117 
color-reactions  of,  II7 
general  precipitants  of,  I18 

reactions  of,  1 17 
separation   and  identification  of, 

139 
Proteoses,  134 
Ptomaines  in  the  urine,  191 
Pulmonary  tuberculosis,  urine  in,  384 
Purdy's  electric  centrifuge,  202 

method  of  quantitating  sugar,  158 
Pus  in  the  urine,  236 

clinical  significance  of,  239 
Donne's  test  for,  239 


Pus-casts,  255 
Putrescin,  222 
Pyelitis,  acute,  331 

calculous,  335 

chronic,  333 
Pyonephrosis,  339 

symptoms  of,  340 

urine  in,  340 
Pyuria,  236 


Quantitative   composition   of    the 

urine,  21 
determination  of  albumin,  130 

of  bile  acids,  181 

of  chlorides,  loi 

of  globulin,  133 

of  hippuric  acid,  82 

of  phosphates,  109 

of  sugar,  155 

of  sulphates,  I12 

of  urea,  47 

of  uric  acid,  66 
Quantity    of    urine    in     twenty-four 
hours,  24 


Reaction  of  the  urine,  31 
Reagents  for  analysis  of  urine,  406 
Receptacles  for  urine.  22 
Records    of     urinary    examinations, 

400 
Red  blood-corpuscles,  230 
Relapsing  fever,  urine  in,  382 
Relative  solids  of  the  urine,  37 
Removal  of  albumin  by  heat,  129 
Renal  calculus,  324 

casts,  247 

embolism,  327 

epithelium,  242 
Retention  of  urine,  25 
Rheumatism,  acute  articular,  urine  in, 

395 


Saccharimeter,  Einhorn's,  160 
Santonin  in  the  urine,  29 
Sarcina  urinse,  265 
Sarcolactic  acid  in  the  urine,  97 
Scarlet  fever,  urine  in,  388 
Scurvy,  urine  in,  397 
Sediment-glass,  204 
Sediments, ammonio-magnesium  phos- 
phate in,  215 

ammonium-urate  in,  211 

amorphous  urates  in,  212 

bilirubin  in,  224 

blood  in,  230 


INDEX. 


415 


Sediments,  calcium  oxalate  in,  217 
phosphate  in,  216 
classitication  of,  207 
cystin  in,  221 
epithelimn  in,  241 
extraneous  substances  in,  261 
fragments  of  tumors  in,  349 
hematoidin  in,  224 
hippuric  acid  in,  80 
leucin  in,  224 
leucocytes  in,  236 
mounting  of,  262 
nonorganized,  208 
organized,  230 
preparation     of,     for      microscopic 

examination,  206 
pus  in,  236 
renal  casts  in,  247 
spermatozoa  in,  258 
tyrosin  in,  226 
urates  in,  210 
uric  acid  in,  208 
Seminal  cells,  245 
Senile  interstitial  nephritis,  300 
Serum-albumin,  1 18 
Serum-globulin,  132 
Sherer's  test  for  leucin,  225 
Silver   nitrate,  standard  solution   of, 

102 
Skatoxyl-potassium  sulphate,  87 

clinical  significance  of,  88 
Smallpox,  urine  in,  390 
Smegma  bacilli  in  the  urine,  324 
Smoky  color  of  the  urine,  27 
Soda,  chlorinated,  solution  of,  51 
Sodium  chloride,  99 

hypobromite,  solution  of,  52 
nitrite,  182.     See  Ehrlich' s  Reac- 
tion. 
urate,  210 
Solids  of  the  urine,  37 

by  specific  gravity,  40 
determination  of,  39 
relative  and  absolute,  37 
Specific  gravity,  34 

causes  of  variation,  34 
method  of  taking,  37 
Spermatozoa  in  the  urine,  258 

detection  of,  259 
Squibb' s  apparatus  for  urea,  50 
Staining  of  tubercle  bacilli,  323 

of  gonococci,  266 
Standard  solution  of  barium  chloride, 

113 

of  nitrate  of  silver,  1 02 
of  uranium  nitrate,  109 
Subacute  glomerular  nephritis,  300 
Succinic  acid  in  the  urine,  97 
Sugar  in  the  urine,  145 


Sugar  in  the  urine,  detection  of,  146 

quantitative  determination  of,  155 
Sulphanilic  acid,  182.    See  EhrlicIC s 

Reaction. 
Sulphates  in  the  urine.  III 

clinical  significance  of,  112 

detection  of,  112 

ethereal,  83 

quantitative     detemiination     of, 
112,  114 
Sulphuretted  hydrogen  in  the  urine, 

31 

Tabular    arrangement   of    Heller's 

tests,  402 
Tsenia  echinococcus,  269 
Teichmann's  test  for  blood  pigment, 

235 

crystals,  236 
Temporary  glycosuria,  368,  37  : 
Tests,  chemical,  order  of  application 
of,  403 

for  albumin,  122.  125 
Total  solids,  38 
Toxicity  of  the  urine,  196 
Transparency  of  the  urine,  29 
Traumatic  glycosuria,  369 
Tribromphenol,  89 
Triple  phosphate,  crystals  of,  215 
Trommer's  test  for  sugar,  147 
Trypsin  in  the  urine,  98 
Tubercle  bacilli  in  the  urine,  detec- 
tion of,  323 
Tuberculosis,  local  caseating,  321 

of  the  bladder,  346 

of  the  kidneys,  321 

of  the  prostate,  356 

pulmonary,  urine  in,  384 
Tumors  of  the  bladder,  348 

of  the  kidney,  328 
Turbidity  due  to  amorphous  urates,  30 

due  to  bacteria,  30 

due  to  earthy  phosphates,  29 
Typhoid  fever,   urine  in,  380 
Typhus  fever,  urine  in,   382 
Tyrosin,  226 

clinical  significance  of,  228 

detection  of,  226 


Uhle,   table  of,  44 

Uranium  nitrate,  standard  solution  of, 

109 
Urates,  210 
Urea,  detection  of,  47 

ferment,  t^t, 

oxalate,  41 

phosphate,  41 


416 


INDEX. 


Urea,  properties  of,  41 

quantitative  determination  of,  47 

theory  of  formation  of,  43 
Uremia,  365 
Ureometer,  Doremus',  56 

Hinds',  57 
Ureteral  epithelium,  244 
Ureteritis,   341 
Urethral  epithelium,  245 
Urethritis,   357 
Uric  acid,  59 

clinical  significance  of,  65,  213 
crystals  of,  208 
decomposition  products  of,  61 
detection  of,  66 

quantitative  determination  of,  66 
properties  of,  61 
Urinary  coloring-matters,  90 

concretions,  270 

chemic  examination  of,   280 
composition  of,   272 

constituents,  Parkes'   table  of,  21 

sediments,    199 

method  of  obtaining,   200 
Urine,  abnormal  constituents  of,  117 

alkalinity  of,  32 

ammoniacal  decomposition  of,  ^3 

analysis  of,  apparatus  for,  406 

black,  28 

color  of,  25 

glass,  204 

increased  acidity  of,   34 
quantity  of,   24 

inorganic  constituents  of,  99 

normal,    21 

odor  of,   30 

of  chronic  disease,  379 

organic  constituents  of,  41 

preservatives  for,  23 

reaction  of,  31 

reagents  for  analysis  of,  406 

receptacles  for,   22 

relative  solids  of,  37 

retention  of,  25 

solids  of,   37 

specific  gravity  of,  34 

toxicity  of,   196 

transparency  of,  29 

turbidity  of,    29 
Urinometer,  35 

glass,  35 


Urinous  odor,  30 

Urobilin,  clinical  significance  of,  92 

detection  of,  92 

normal,  90 
•  origin  of,  90 

pathologic,  90 
Urochrome,  92 

detection  of,  93 
Uroerythrin,  94 

detection  of,  95 

significance  of,  94 
Urophxin  test,  92 
Urorosein,  95 

detection  of,  95 
Urostealith  calculi,  279 


Vaginal  discharge  in  the  urine,  241, 
246 
epithelium,  246 

Vegetable  substances  in  the  urine,  28 

Vesical  calculus,  344 

Villous  tumor  of  the  bladder,  348 

Vogel's  scale  of  colors,  26 

Volatile  acids,  30 

Volhard  and  Falck's  method  of  esti- 
mating chlorine,  104 


Waxy  casts,  251 

Weidel's  reaction  for  heteroxanthin, 

75 
for  paraxanthin,  75 
Weyl's  test  for  kreatinin,  79 


Xanthin,  72 

bases,  71 

isolation  of,  75 

concretions,  278 

detection  of,  73 
Xanthoproteic  reaction,  117 


Yeast  fungus  in  the  urine,  264 
Yellow  atrophy  of  the  liver,   acute, 

392 
fever,  urine  in,  381 
Yvon  and  Berlioz,  comparative  table 
of,  22 


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Professor  of  Hygiene  and  Bacteriology,  University  of  Pennsylvania. 
Octavo,  351  pages,  with  numerous  illustrations.     Cloth,  $2.50  net. 


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Anders*  Practice  qf  Medicine.       Fifth  Revised  Edition. 

A  Text-Book  of  the  Practice  of  Medicine.  By  James  M.  Anders, 
M.  D.,  Ph.  D.,  LL.  D.,  Professor  of  the  Practice  of  Medicine  and  of 
Chnical  Medicine,  Medico-Chirurgical  College,  Philadelphia.  Hand- 
some octavo  volume  of  1292  pages,  fully  illustrated.  Cloth,  $5.50  net; 
Sheep  or  Half  Morocco,  $6.50  net. 

Bastin's  Botany. 

Laboratory  Exercises  in  Botany.  By  Edson  S.  Bastin,  M.  A.,  late 
Professor  of  Materia  Medica  and  Botany,  Philadelphia  College  of 
Pharmacy.     Octavo,  536  pages,  with  87  plates.     Cloth,  $2.00  net. 

Beck  on  Fractures. 

Fractures.  By  Carl  Beck,  M.  D.,  Surgeon  to  St.  Mark's  Hospital  and 
the  New  York  German  Poliklinik,  etc.  With  an  appendix  on  the  Prac- 
tical Use  of  the  Rontgen  Rays.  335  pages,  170  illustrations.  Cloth, 
$3.50  net. 

Beck's  Surgical  Asepsis. 

A  Manual  of  Surgical  Asepsis.  By  Carl  Beck,  M.  D.,  Surgeon  to  St. 
Mark's  Hospital  and  the  New  York  German  Poliklinik,  etc.  306  pages; 
65  text-illustrations  and  12  full-page  plates.     Cloth,  $1.25  net. 

Boisliniere's    Obstetric   Accidents,   Emergencies,  anb 
Operations. 

Obstetric  Accidents,  Emergencies,  and  Operations.  By  L.  Ch.  Bois- 
liniere,  M.  D.,  late  Emeritus  Professor  of  Obstetrics,  St.  Louis  Medical 
College.      381  pages,  handsomely  illustrated.     Cloth,  $2.00  net. 

Bohm,  Davidoff,   and  Huber's  Histology. 

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By  Dr.  A.  A.  Bohm  and  Dr.  M.  von  Davidoff,  of  Munich,  and 
G.  Carl  Huber,  M.  D.,  Junior  Professor  of  Anatomy  and  Director  of 
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Butler's  Materia  Medica,  Therapeutics,  and  Pharma- 
cology.     Third  Edition,  Revised. 

A  Text-Book  of  Materia  Medica,  Therapeutics,  and  Pharmacology. 
By  George  F.  Butler,  Ph.  G.,  M.  D.,  Professor  of  Materia  Medica  and 
of  Clinical  Medicine,  College  of  Physicians  and  Surgeons,  Chicago. 
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Cerna  on  the  Newer  Remedies,    second  Edition.  Revised. 

Notes  on  the  Newer  Remedies,  their  Therapeutic  Applications  and 
Modes  of  Administration.  By  David  Cerna,  M.  D.,  Ph.  D.,  Demon- 
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OF   W.  B.  SAUNDERS   6-    CO. 


Chapin  on  Insanity. 

A  Compendium  of  Insanity.  By  John  B.  Chapin,  M.  D.,  LL.  D., 
Physician-in-Chief,  Pennsylvania  Hospital  for  the  Insane :  Honorary 
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trated.    Cloth,  §1.25   net. 

Chapman's   Medical    Jurisprudence  and  Toxicology. 

Second  Edition,  Revised. 

Medical  Jurisprudence  and  Toxicology.  By  Henry  C.  Chapman, 
M.  D.,  Professor  of  Ins-titutes  of  Medicine  and  Medical  Jurisprudence, 
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trations and  3  full-page  plates  in  colors.     Cloth,  $1.50  net. 

Church  and  Peterson's  Nervous  and  Mental  Diseases. 

Third  Edition.  Revised  and  Enlarged. 

Nervous  and  Mental  Diseases.  By  Archibald  Church,  M.  D.,  Pro- 
fessor of  Nervous  and  Mental  Diseases,  and  Head  of  the  Neurological 
Department,  Northwestern  University  Medical  School,  Chicago ;  and 
Frederick  Peterson,  M.  D.,  Chief  of  Clinic,  Nervous  Department, 
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volume  of  875  pages,  profusely  illustrated.  Cloth,  $5.00  net;  Sheep  or 
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Clarkson's  Histology. 

A  Text-Book  of  Histology,  Descriptive  and  Practical.  By  Arthur 
Clarkson,  M.  B.,  CM.  Edin.,  formerly  Demonstrator  of  Physiology 
in  the  Owen's  College,  Manchester;  late  Demonstrator  of  Physiology 
in  Yorkshire  College,  Leeds.  Large  octavo,  554  pages;  22  engravings 
and  174  beautifully  colored  original  illustrations.     Cloth,  $4.00  net. 

Corwin's  Physical  Diagnosis.    Third  Edition.  Revised. 

Essentials  of  Physical  Diagnosis  of  the  Thorax.  By  Arthur  M. 
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Medical  College,  Chicago.    219  pages,  illustrated.     Cloth,  $1.25  net. 

CrOOkshank's    Bacteriology.       Fourth  Edition.  Revised. 

A  Text-Book  of  Bacteriology.  By  Edgar  M.  Crookshank,  M.  B., 
Professor  of  Comparative  Pathology  and  Bacteriology,  King's  College, 
London.  Octavo,  700  pages,  273  engravings  and  22  original  colored 
plates.     Cloth,  $6.50  net;    Half  Morocco,  §7. 50  net. 

DaCosta'S    Surgery.       Third  Edition.  Revised. 

Modern  Surgery,  General  and  Operative.  By  John  Chalmers  Da 
Costa,  M.  D.,  Professor  of  Principles  of  Surgery  and  Clinical  Surgery, 
Jefferson  Medical  College,  Philadelphia  ;  Surgeon  to  the  Philadelphia 
Hospital,  etc.  Handsome  octavo  volume  of  11 17  pages,  profusely 
illustrated.     Cloth,  $5.00  net;    Sheep  or  Half  Morocco,  $6.00  net. 

Enlarged  by  over  200  Pages,  with  more  than  100  New  Illustrations. 


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Davis's  Obstetric  Nursing. 

Obstetric  and  Gynecologic  Nursing.  By  Edward  P.  Davis,  A.  M., 
M.  D.,  Professor  of  Obstetrics  in  Jefferson  Medical  College  and  the 
Philadelphia  Polyclinic ;  Obstetrician  and  Gynecologist  to  the  Phila- 
delphia Hospital.  i2mo  volume  of  400  pages,  fully  illustrated. 
Crushed  Buckram,  $1.75   net. 

DeSchweinitz  on  Diseases  qf  the  Eye.   Third  Edition,  Revised. 

Diseases  of  the  Eye.  A  Handbook  of  Ophthalmic  Practice.  By  G. 
E.  DE  ScHWEiNiTZ,  M.  D.,  Profcssor  of  Ophthalmology,  Jefferson  Medi- 
cal College,  Philadelphia,  etc.  Handsome  royal  octavo  volume  of  696 
pages;  256  fine  illustrations  and  2  chromo-lithographic  plates.  Cloth, 
$4.00  net;  Sheep  or  Half  Morocco,  $5.00  net. 

Dorland's  Dictionaries. 

[See  American  Illustrated  Medical  Dictionary  and  American 
Pocket  Medical  Dictionary  on  page  3.] 

Dorland's    Obstetrics.       second  Edition,  Revised  and  Greatly  Enlarged. 

Modern  Obstetrics.  By  W.  A.  Newman  Dorland,  M.  D.,  Assistant 
Demonstrator  of  Obstetrics,  University  of  Pennsylvania;  Associate  in 
Gynecology,  Philadelphia  Polyclinic.  Octavo  volume  of  797  pages, 
with  201  illustrations.     Cloth,  $4.00  net. 

Eichhorst's  Practice  gf   Medicine. 

A  Text-Book  of  the  Practice  of  Medicine.  By  Dr.  Herman  Eichhorst, 
Professor  of  Special  Pathology  and  Therapeutics  and  Director  of  the 
Medical  Clinic,  University  of  Zurich.  Translated  and  edited  by  Augus- 
tus A.  EsHNER,  M.  D.,  Professor  of   Clinical   Medicine,  Philadelphia 

Polyclinic.    Two  octavo  volumes  of  600  pages  each,  over  150  illustrations. 

Prices  per  set :   Cloth,  $6.00  net ;  Sheep  or  Half  Morocco,  $7.50  net. 

Friedrich  and  Curtis  on  the  Nose,  Throat,  and  Ear. 

Rhinology,  Laryngology,  and  Otology,  and  Their  Significance  in  Gen- 
eral Medicine.  By  Dr.  E.  P.  Friedrich,  of  Leipzig.  Edited  by  H. 
HoLBROOK  Curtis,  M.  D.,  Consulting  Surgeon  to  the  New  York  Nose 
and  Throat  Hospital.     Octavo,  348  pages.     Cloth,  $2.50  net. 

Frothingham's  Guide  for  the  Bacteriologist. 

Laboratory  Guide  for  the  Bacteriologist.  By  Langdon  Frothingham, 
M.  D.  v.,  Assistant  in  Bacteriology  and  Veterinary  Science,  Sheffield 
Scientific  School,  Yale  University.     Illustrated.     Cloth,  75  cts.  net. 

Garrigues*  Diseases  qf  Women.     Third  Edition.  Revised. 

Diseases  of  Women.  By  Henry  J.  Garrigues,  A.  M.,  M.  D.,  Gyne- 
cologist to  St.  Mark's  Hospital  and  to  the  German  Dispensary,  New 
York  City.  Octavo,  756  pages,  with  367  engravings  and  colored  plates. 
Cloth,  $4.50  net;  Sheep  or  Half  Morocco,  $5.50  net. 


OF    W.  B.  SAUNDERS   &^    CO. 


Gould  and  Pyle's  Curiosities  of  Medicine. 

Anomalies  and  Curiosities  of  Medicine.  By  George  M.  Gould,  M.D., 
and  Walter  L.  Pyle,  M.  D.  An  encyclopedic  collection  of  rare  and 
extraordinary  cases  and  of  the  most  striking  instances  of  abnormality  in 
all  branches  of  Medicine  and  Surgery,  derived  from  an  exhaustive 
research  of  medical  literature  from  its  origin  to  the  present  day, 
abstracted,  classified,  annotated,  and  indexed.  Handsome  octavo 
volume  of  968  pages;  295  engravings  and  12  full-page  plates.  Popular 
Edition.      Cloth,  $3.00  net;  Sheep  or  Half  Morocco,  54.00  net. 

r 

Grafstrom's  Mechano-Therapy. 

A  Text-Book  of  Mechano-Therapy  (Massage  and  Medical  Gymnastics). 
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pital, Blackwell's  Island,  New  York.  i2mo,  139  pages,  illustrated. 
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Griffith    on    the    Baby.       second  Edition.  Revised. 

The  Care  of  the  Baby.  By  J.  P.  Crozer  Griffith,  M.  D.,  Clinical 
Professor  of  Diseases  of  Children,  University  of  Pennsylvania ;  Phy- 
sician to  the  Children's  Hospital,  Philadelphia,  etc.  i2mo,  404  pages; 
67  illustrations  and  5  plates.     Cloth,  ^1.50  net. 

Griffith's  Weight  Chart. 

Infant's  Weight  Chart.  Designed  by  J.  P.  Crozer  Griffith,  M.  D., 
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25  charts  in  each  pad.     Per  pad,   50  cts.  net. 

Hart's  Diet  in  Sickness  and  in  Health. 

Diet  in  Sickness  and  Health.  By  Mrs.  Ernest  Hart,  formerly  Student 
of  the  Faculty  of  Medicine  of  Paris  and  of  the  London  School  of  Medi- 
cine for  Women ;  with  an  Introduction  by  Sir  Henry  Thompson, 
F.  R.  C.  S.,  M.  D.,  London.      220  pages.     Cioth,  $1.50  net. 

Haynes*  Anatomy. 

A  Manual  of  Anatomy.  By  Irving  S.  Haynes,  M.  D.,  Professor  of 
Practical  Anatomy  in  Cornell  University  Medical  College.  680  pages ; 
42  diagrams  and  134  full-page  half-tone  illustrations  from  original  photo- 
graphs of  the  author's  dissections.     Cloth,  $2.50  net. 

Heisler'S    Embryology.       second  Edition.  Revised, 

A  Text-Book  of  Embryology.  By  John  C.  Heisler,  M.  D.,  Professor 
of  Anatomy,  Medico-Chirurgical  College,  Philadelphia.  Octavo  volum.e 
of  405  pages,  handsomely  illustrated.     Cloth,  $2.50  net. 

Hirst's    Obstetrics.       Third  Edition.  Revised  and  Enlarged. 

A  Text-Book  of  Obstetrics.  By  Barton  Cooke  Hirst,  M.  D.,  Professor 
of  Obstetrics,  University  of  Pennsylvania.  Handsome  octavo  volume 
of  873  pages  ;  704  illustrations,  36  of  them  in  colors.  Cloth,  $5.00  net; 
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Hyde  and  Montgomery  on   Syphilis  and  the  Venereal 

Diseases.       second  Edition,  Revised  and  Greatly  Enlarged. 

Syphilis  and  the  Venereal  Diseases.  By  James  Nevins  Hyde,  M.  D., 
Professor  of  Skin  and  Venereal  Diseases,  and  Frank  H.  Montgomery, 
M.  D.,  Associate  Professor  of  Skin,  Genito-Urinary,  and  Venereal  Dis- 
eases in  Rush  Medical  College,  Chicago,  111.  Octavo,  594  images, 
profusely  illustrated.     Cloth,  $4.00  net. 

*Pte  International  Text- Book  of  Surgery,    in  Two  volumes. 

By  American  and  British  Authors.  Edited  by  J.  Collins  Warren, 
M.  D.,  LL.  D.,  F.  R.  C.  S.  (Hon.),  Professor  of  Surgery,  Harvard  Medi- 
cal School,  Boston ;  and  A.  Pearce  Gould,  M.  S.,  F.  R.  C.  S.,  Lecturer 
on  Practical  Surgery  and  Teacher  of  Operative  Surgery,  Middlesex 
Hospital  Medical  School,  London,  Eng.  Vol.  L  General  Surgery. — 
Handsome  octavo,  947  pages,  with  458  beautiful  illustrations  and  9 
lithographic  plates.  Vol.  IL  Special  or  Regional  Surgery. — Handsome 
octavo,  1072  pages,  with  471  beautiful  illustrations  and  8  lithographic 
plates.  Sold  by  Subscription.  Prices  per  volume :  Cloth,  $5.00  net; 
Sheep  or  Half  Morocco,  $6.00  net. 

"  It  is  the  most  valuable  work  on  the  subject  that  has  appeared  in  some  years.  The  clini- 
cian and  the  pathologist  have  joined  hands  in  its  production,  and  the  result  must  be  a  satis- 
faction to  the  editors  as  it  is  a  gratification  to  the   conscientious  reader." — Annals  of  Surgery. 

"  This  is  a  work  which  comes  to  us  on  its  own  intrinsic  merits.  Of  the  latter  it  has  very 
many.  The  arrangement  of  subjects  is  excellent,  and  their  treatment  by  the  different  authors 
is  equally  so.  What  is  especially  to  be  recommended  is  the  painstaking  endeavor  of  each 
writer  to  make  his  subject  clear  and  to  the  point.  To  this  end  particularly  is  the  technique 
of  operations  lucidly  described  in  all  necessary  detail.  And  withal  the  work  is  up  to  date  in 
a  very  remarkable  degree,  many  of  the  latest  operations  in  the  different  regional  parts  of  the 
body  being  given  in  full  details.  There  is  not  a  chapter  in  the  work  from  which  the  reader 
may  not  learn  something  new." — Medical  Record,  New  York. 

Jackson's  Diseases  qf  the  "Eye, 

A  Manual  of  Diseases  of  the  Eye.  By  Edward  Jackson,  A.  M.,  M.  D., 
Emeritus  Professor  of  Diseases  of  the  Eye,  Philadelphia  Polyclinic  and 
College  for  Graduates  in  Medicine.  i2mo  volume  of  535  ])ages,  with 
178  illustrations,  mostly  from  drawings  by  the  author.    Cloth,  $2.50  net. 

Keating's  Life  Insurance. 

How  to  Examine  for  Life  Insurance.  By  John  M.  Keating,  M.  D., 
Fellow  of  the  College  of  Physicians  of  Philadelphia  ;  Ex-President  of  the 
Association  of  Life  Insurance  Medical  Directors.  Royal  octavo,  211 
pages.     With  numerous  illustrations.     Cloth,  $2.00  net. 

Keen  on  the  Surgery  qf  Typhoid  Fever. 

The  Surgical  Complications  and  Sequels  of  Typhoid  Fever.  By  Wm. 
W.  Keen,  M.  D.,  LL.  D.,  F.  R.  C.  S.  (Hon.),  Professor  of  the  Principles 
of  Surgery  and  of  Clinical  Surgery,  Jefferson  Medical  College,  Phila- 
delphia, etc.    Octavo  volume  of  386  pages,  illustrated.    Cloth,  $3.00  net. 

Keen's    Operation    Blank.       second  Edition,  Revised  Form. 

An  Operation  Blank,  with  Lists  of  Instruments,  etc.,  Required  in  Vari- 
ous Operations.  Prepared  by  W.  W.  Keen,  M.  D.,  LL.  D.,  F.  R.  C.  S. 
(Hon.),  Professor  of  the  Principles  of  Surgery  and  of  Clinical  Surgery, 
Jefferson  Medical  College,  Philadelphia.  Price  per  pad,  blanks  for  fifty 
operations,  50  cts.  net. 


OF    W.  B.  SAUNDERS   &^    CO. 


Kyle  on  ihe  Nose  and  Throat,    second  Edition. 

Diseases  of  the  Nose  and  Throat.  By  D.  Eraden  Kyle,  M.  D.,  Clinical 
Professor  of  Laryngology  and  Rhinology,  Jefferson  Medical  College, 
Philadelphia.  Octavo,  646  pages;  over  150  illustrations  and  6  litho- 
graphic plates.     Cloth,  $4.00  net;  Sheep  or  Half  Morocco,  $5.00  net. 

Laine's  Temperature  Chart. 

Temperature  Chart.  Prepared  by  D.  T.  Laine,  M.  D.  Size  8x13!/^ 
inches.  A  conveniently  arranged  Chart  for  recording  Temperature, 
with  columns  for  daily  amounts  of  Urinary  and  Fecal  Excretions,  Food' 
Remarks,  etc.  On  the  back  of  each  chart  is  given  the  Brand  treatment 
of  Typhoid  Fever.     Price,  per  pad  of  25  charts,  50  cts.  net. 

Levy,  Klemperer,  anb  Eshner's  Clinical  Bacteriology. 

The  Elements  of  Clinical  Bacteriology.  By  Dr.  Ernst  Levy,  Pro- 
fessor in  the  University  of  Strasburg,  and  Felix  Klemperer,  Privat- 
docent  in  the  University  of  Strasburg.  Translated  and  edited  by 
Augustus  A.  Eshner,  M.  D.,  Professor  of  Clinical  Medicine,  Philadel- 
phia Polyclinic.     Octavo,  440  pages,  fully  illustrated.     Cloth,  ^2.50  net. 

Lockwood's  Practice  cf  Medicine.         Revfs^d^^nd'^SSed. 

A  Manual  of  the  Practice  of  Medicine.  By  George  Roe  Lockwood, 
M.  D.,  Professor  of  Practice  in  the  Woman's  Medical  College  of  the 
New  York  Infirmary,  etc. 

Long's  Syllabus  of  Gynecology. 

A  Syllabus  of  Gynecology,  arranged  in  Conformity  with  "An  American 
Text-Book  of  Gynecology."  By  J.  W.  Long,  ]\L  D.,  Professor  of  Dis- 
eases of  Women  and  Children,  Medical  College  of  Virginia,  etc.  Cloth, 
interleaved,  $1.00  net. 

Macdonald*s  Surgical  Diagnosis  and  Treatment. 

Surgical  Diagnosis  and  Treatment.  By  J.  W.  Macdonald,  M.  D. 
Edin.,  F.  R.  C.  S.  Edin.,  Professor  of  Practice  of  Surgery  and  Clinical 
Surgery,  Hamline  University.  Handsome  octavo,  800  images,  fully  illus- 
trated.    Cloth,  1^5.00  net;  Sheep  or  Half  Morocco,  ;^6.oo  net. 

Mallory  and  Wright's  Pathological  Technique. 

Second  Edition.  Revised. 

Pathological  Techni(]ue.  A  Practical  Manual  for  Laboratory  Work  in 
Pathology,  Bacteriology,  and  Morbid  Anatomy,  with  chapters  on  Post- 
Mortem  Technique  and  the  Performance  of  Autopsies.  By  Frank  B. 
Mallory,  A.  M.,  M.  D.,  Assistant  Professor  of  Pathology,  Harvard 
University  Medical  School,  Boston;  and  James  H.  Wright,  A.M., 
M.  D.,  Instructor  in  Pathology,  Harvard  University  Medical  School, 
Boston. 

McFarland's  Pathogenic  Bacteria.   '''tz.l^o::yZ'V:A!^ 

Text-Book  upon  the  Pathogenic  Bacteria.  By  Joseph  McFarland, 
M.  D.,  Professor  of  Pathology  and  Bacteriology,  Medico-Chirurgical 
College  of  Philadelphia,  etc.  Octavo  volume  of  621  pages,  finely  illus- 
trated.    Cloth,  $3.25  net. 


MEDICA  L   P  UBL ICA  TIONS 


Mei^s  on  Feeding  in  Infancy. 

Feeding  in  Early  Infancy.  By  Arthur  V.  Meigs,  M.  D.  Bound  in 
limp  cloth,  flush  edges,  25  cts.  net. 

Moore's  Orthopedic  Surgery. 

A  Manual  of  Orthopedic  Surgery.  By  James  E.  Moore,  M.  D.,  Pro- 
fessor of  Orthopedics  and  Adjunct  Professor  of  Clinical  Surgery,  Uni- 
versity of  Minnesota,  College  of  Medicine  and  Surgery.  Octavo  volume 
of  356  pages,  handsomely  illustrated.     Cloth,  $2.50  net. 

Morten's  Nurses*  Dictionary. 

Nurses'  Dictionary  of  Medical  Terms  and  Nursing  Treatment.  Con- 
taining Definitions  of  the  Principal  Medical  and  Nursing  Terms  and 
Abbreviations  ;  of  the  Instruments,  Drugs,  Diseases,  Accidents,  Treat- 
ments, Operations,  Foods,  Appliances,  etc.  encountered  in  the  ward  or 
in  the  sick-room.  By  Hoxnor  Morten,  author  of  "How  to  Become 
a  Nurse,"  etc.      r6mo,  140  pages.     Cloth,  $1.00  net. 

Nancrede*s  Anatomy  and  Dissection.    Fourth  Edition. 

Essentials  of  Anatomy  and  Manual  of  Practical  Dissection.  By  Charles 
B.  Nancrede,  M.  D.,  LL.  D.,  Professor  of  Surgery  and  of  Clinical  Sur- 
gery, University  of  Michigan,  Ann  Arbor.  Post-octavo,  500  pages,  with 
full-page  lithographic  plates  in  colors  and  nearly  200  illustrations.  Extra 
Cloth  (or  Oilcloth  for  dissection-room),  ^2.00  net. 

Nancrede's  Principles  qf  Surgery. 

Lectures  on  the  Principles  of  Surgery.  By  Chas.  B.  Nancrede,  M.  D., 
LL.  D.,  Professor  of  Surgery  and  of  Clinical  Surgery,  LTniversity  of 
Michigan,  Ann  Arbor.   Octavo,  398  pages,  illustrated.    Cloth,  $2.50  net. 

Norris*s  Syllabus  qf  Obstetrics.    Third  Edition,  Revised. 

Syllabus  of  Obstetrical  Lectures  in  the  Medical  Department  of  the 
University  of  Pennsylvania.  By  Richard  C.  Norris,  A.  M.,  M.  D., 
Instructor  in  Obstetrics  and  Lecturer  on  Clinical  and  Operative  Obstet- 
rics, University  of  Pennsylvania.  Crown  octavo,  222  pages.  Cloth, 
interleaved  for  notes,  S2.00  net. 

Ogden  on  the  Urine. 

Clinical  Examination  of  the  Urine  and  Urinary  Diagnosis.  A  Clinical 
Guide  for  the  Use  of  Practitioners  and  Students  of  Medicine  and  Sur- 
gery. By  J.  Bergen  Ogden,  M.  D.,  Instructor  in  Chemistry,  Harvard 
Medical  School.  Handsome  octavo,  416  pages,  with  54  illustrations 
and  a  number  of  colored  plates.     Cloth,  $3.00  net. 

Penrose's  Diseases  qf  Women.    Fourth  Edition.  Revised. 

A  Text-Book  of  Diseases  of  Women.  By  Charles  B.  Penrose,  M.  D., 
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OF   W.  B.  SAUNDERS   &    CO. 


Pryor — Pelvic  Inflammations. 

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i2mo,  248  pages,  handsomely  illustrated.     Cloth,  $2.00  net. 

Pye's  Bandaging. 

Elementary  Bandaging  and  Surgical  Dressing.  With  Directions  con- 
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Pyle's  Personal  Hygiene. 

A  Manual  of  Personal  Hygiene.  Proper  Living  upon  a  Physiologic 
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Wills  Eye  Hospital,  Philadelphia.  Octavo  volume  of  344  pages,  fully 
illustrated.     Cloth,  $1.50  net. 

_-  -,       -^,  .     I       ,  Second  Edition, 

Raymond  S    Physiology.       Revised  and  Greatly  Enlarged. 

A  Text-Book  of  Physiology.  By  Joseph  H.  Raymond,  A.  M.,  M.  D., 
Professor  of  Physiology  and  Hygiene  and  Lecturer  on  Gynecology  in 
the  Long  Island  College  Hospital. 

Salinger  and  Kalteyer*s  Modern  Medicine. 

Modern  Medicine.     By  Julius  L.  Salinger,  M.  D.,  Demonstrator  of 
Clinical  Medicine,   Jefferson  Medical  College;    and  F.  J.   Kalteyer 
M.  D.,  Assistant  Demonstrator  of  Clinical  Medicine,  Jefferson  Medical 
College.     Handsome  octavo,  801  pages,  illustrated.     Cloth,  $4.00  net. 

Saundby's  Renal  anT^  Urinary  Diseases. 

Lectures  on  Renal  and  Urinary  Diseases.  By  Robert  Saundby,  M.  D. 
Edin  Fellow  of  the  Royal  College  of  Physicians,  London,  and  of  the 
Royal  Medico-Chirurgical  Society;  Professor  of  Medicme  m  Mason 
College,  Birmingham,  etc.  Octavo,  434  pages,  with  numerous  illustra- 
tions and  4  colored  plates.     Cloth,  $2.50  net. 

Saunders*  Medical  Hand-Atlases. 

See  pages  1 6  and  !?• 

Saunders*  Pocket  Medical  Formulary,  sixth  Edition.  Revised. 

Bv  William  M.  Powell,  M.  D.,  author  of  ''Essentials  of  Diseases  of 
Children":  Member  of  Philadelphia  Pathological  Society.  Contain- 
incr  1844  formulae  from  the  best-known  authorities.  With  an  Appendix 
containing  Posological  Table,  Formulee  and  Doses  for  Hypodermic 
Medication,  Poisons  and  their  Antidotes,  Diameters  of  the  Female  Pelvis 
and  Fetal  Head,  Obstetrical  Table,  Diet  List  for  Various  Diseases,  Mate- 
rials and  Drugs  used  in  Antiseptic  Surgery,  Treatment  of  Asphyxia  from 
Drowning,  Surgical  Remembrancer,  Tables  of  Incompatibles,  Eruptive 
Fevers,  etc.,  etc.  Handsomely  bound  in  flexible  morocco,  with  side 
index, 'wallet,  and  flap.     $2.00  net. 

Saunders*  Question-Compends. 

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Scudder's    Fractures.       second  Edition.  RevUed. 

The  Treatment  of  Fractures.  By  Chas.  L.  Scudder,  M.  D.,  Assistant 
in  Clinical  and  Operative  Surgery,  Harvard  University  Medical  School. 
Octavo,  460  pages,  with  nearly  600  original  illustrations.  Polished 
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Senn's  Genito-Urinary  Tuberculosis. 

Tuberculosis  of  the  Genito-Urinary  Organs,  Male  and  Female.  By 
Nicholas  Senn,  M.  D.,  Ph.  D.,  LL.  D.,  Professor  of  the  Practice  of 
Surgery  and  of  Clinical  Surgery,  Rush  Medical  College,  Chicago. 
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Senn*s  Practical  Surgery. 

Practical  Surgery.  By  Nicholas  Senn,  M.  D.,  Ph.  D.,  LL.  D.,  Pro- 
fessor of  the  Practice  of  Surgery  and  of  Clinical  Surgery,  Rush  Medical 
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formity with  "An  American  Text-Book  of  Surgery."  By  Nicholas 
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of  Clinical  Surgery,  Rush  Medical  College,  Chicago.     Cloth,  $1.50  net. 

Senn'S    Tumors.      second  Edition,  Revised. 

Pathology  and  Surgical  Treatment  of  Tumors.  By  Nicholas  Senn,  M.  D.  , 
Ph.  D.,  LL.  D.,  Professor  of  the  Practice  of  Surgery  and  of  Clinical 
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Starr's  Diets  for  Infants  and  Children. 

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Children."  230  blanks  (pocket-book  size),  perforated  and  neatly  bound 
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Stengel  and  White  on  the  Blood. 

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Stengel,  M.  D.,  Professor  of  Clinical  Medicine,  University  of  Penn- 
sylvania ;  and  C.  Y.  White,  Jr.,  M.  D.,  Instructor  in  Clinical  Medicine, 
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OF   W.  B.   SAUNDERS   6-    CO.  13 


Stevens*  Therapeutics.      TWrd  Edition.  Revised  and  Greatly  Enlarged. 

A  Text-Book  of  Modern  Therapeutics.  \\y  A.  A.  Stkvkns.  A.  ^[.,  M.  D., 
Lecturer  on  Physical  Diagnosis  in  the  University  of  Pennsylvania. 

Stevens'  Practice  qf  Medicine.     Fifth  Edition.  Revised. 

A  Manual  of  the  Practice  of  Medicine.  By  A.  A.  Stevens,  A.  M., 
M.  D.,  Lecturer  on  Physical  Diagnosis  in  the  University  of  Pennsyl- 
vania. Specially  intended  for  students  preparing  for  graduation  and 
hospital  examinations.  Post-octavo,  519  pages;  illustrated.  Flexible 
Leather,  $2.00  net. 

Stewart's    Physiologfy.       Fourth  Edition.  Revised. 

A  Manual  of  Physiology,  with  Practical  Exercises.  For  Students  and 
Practitioners.  By  G.  N.  Stewart,  M.  A.,  M.  D.,  D.  Sc,  Professor  of 
Physiology  in  the  Western  Reserve  L^niversity,  Cleveland,  Ohio.  Octavo 
volume  of  894  pages ;  336  illustrations  and  5  colored  plates.  Cloth, 
$3-75  net. 

Stoney's  Materia  Medica  for  Nurses. 

Materia  Medica  for  Nurses.  By  Emily  A.  M.  S toney,  late  Superintend- 
ent of  the  Training-School  for  Nurses,  Carney  Hospital,  South  Boston, 
Mass.     Handsome  octavo  volume  of  306  pages.     Cloth,  $1.50  net. 

StOney'S    Nursing.       second  Edition,  Revised. 

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A.  M.  Stoney,  late  Superintendent  of  the  Training-School  for  Nurses, 
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Stoney's  Surgical  Technic  for  Nurses. 

Bacteriology  and  Surgical  Technic  for  Nurses.  By  Emily  A.  M.  Stoney, 
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South  Boston,  Mass.     i2mo  \olunie,  fully  illustrated.     Cloth,  ^1.25  net. 

Thomas's    Diet    Lists.       second  Edition.  Revised. 

Diet  Lists  and  Sick-Room  Dietary.  By  Jerome  B.  Tho:\ias,  ]\L  D., 
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Thornton's  Dose-Book  and  Prescription-Writing. 

Second  Edition,  Revised  and  Enlarged. 

Dose-Book  and  Manual  of  Prescription- Writing.  By  E.  Q.  Thornton, 
M.  D.,  Demonstrator  of  Therapeutics,  Jefferson  Medical  College,  Phila- 
delphia. 

Van  Valzah  and  Nisbet's  Diseases  qf  the  Stomach. 

Diseases  of  the  Stomach.  By  William  W.  Van  Valzah,  M.  D.,  Pro- 
fessor of  General  Medicine  and  Diseases  of  the  Digestive  System  and 
the  Blood,  New  York  Polyclinic;  and  J.  Douglas  Nisbet,  M.  D., 
Adjunct  Professor  of  General  Medicine  and  Diseases  of  the  Digestive 
System  and  the  Blood,  New  York  Polyclinic.  Octavo  volume  of  674 
pages,  illustrated.     Cloth,  S3. 50  net. 


14  MEDICAL   PUBLICATIONS. 

Vecki'S    Sexual    Impotence.        second  Edition,  Revbed. 

The  Pathology  and  Treatment  of  Sexual  Impotence.  By  Victor  G. 
Vecki,  M.  D.  From  the  second  German  edition,  revised  and  enlarged. 
Dema-octavo,  291  pages.     Cloth,  ^2.00  net. 

Vierordt'S    Medical     Dia^^nOSiS.       Fourth  Edition,  Revised. 

Medical  Diagnosis.  By  Dr.  Oswald  Vierordt,  Professor  of  Medicine, 
University  of  Heidelberg.  Translated,  with  additions,  from  the  fifth 
enlarged  German  edition,  with  the  author's  pennission,  by  Francis  H. 
Stuart,  A.M.,  M.  D.  Handsome  octavo  volume,  603  pages;  194 
wood-cuts,  many  of  them  in  colors.  Cloth,  $4.00  net;  Sheep  or  Half 
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Watson's  Handbook  for  Nurses. 

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Edition,  under  supervision  of  A.  A.  Stevens,  A.  M.,  M.  D.,  Lecturer 
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Warren's  Surgical  Patholo^.     second  Edition. 

Surgical  Pathology  and  Therapeutics.  By  John  Collins  Warren, 
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Medical  School.  Handsome  octavo,  873  pages;  136  relief  and  litho- 
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1.  Essentials  of  Physiology.     By  Sidney  Budgett,  M.  D.     A  A'ew  Work. 

2.  Essentials  of  Surgery.     By  Edward  Martin,  M.D.     Seventli  edition,  revised,  with 

an  Appendix  and  a  chapter  on  Appendicitis. 

3.  Essentials  of  Anatomy.     By  Charles   B.   Nancrede,   M.  D.     Sixth  edition,  thor- 

ouglily   revised   and  enlarged. 

4.  Essentials  of  Medical  Chemistry,  Organic  and  Inorganic.     By  Lawrence  Wolff, 

M.  IJ.      Fifth  edition,  revised. 

5.  Essentials  of  Obstetrics.     By  W.  Easterly  Ashton,  M.  D.    Fourth  edition,  revised 

and  enlarged. 

45.    Essentials  of  Pathology  and  Morbid  Anatomy.     By  F.  J.  Kai.teyer,  M.  D.     In 

preparation. 

7.  Essentials  of  Materia  Medica,  Therapeutics,  and  Prescription-Writing.    By  Henry 

Morris,  M.  D.     Fiftli  edition,  revised. 

8,  9.    Essentials  of  Practice  of  Medicine.     By  Henry  T^Iorris,  M.  D.     An  Appendix 

on  Urine  E.\amination.  By  Lawrence  Wolff,  M.  D.  Third  edition,  enlarged 
by  some  300  Essential  FormulEe,  selected  from  eminent  autiiorities,  by  Wm.  M. 
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10.  Essentials  of  Gynecology.     By  Edwin  B.  Cragin,  M.  D.     Fifth  edition,  revised. 

11.  Essentials  of  Diseases  of  the  Skin.     By  Henry  W.  Stei.wagon,  M.  D.     Fourth 

edition,  revised  and   enlarged. 

12.  Essentials  of  Minor  Surgery,  Bandaging,  aoid  Venereal    Diseases.     By  Edward 

Martin,  M.  D.     Second  edition,  revised  and  enlarged. 

13.  Esseiitials    of    Legal    Medicine,   Toxicology,   and    Hygiene.     This   volume   is   at 

present  out  of  print. 

14.  Essentials  of  Diseases  of  the  Eye.     By  Edward  Jackson,  M.  D.     Third  edition, 

revised  and  enlarged. 

15.  Essentials  of  Diseases  of  Children.    By  William  M.  Powell,  M.  D.    Third  edition. 

16.  Essentials    of    Examination    of    Urine.     By    Lawrence    Wolff,   RL  D.      Colored 

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17.  Essentials  of  Diagnosis.     By  S.   Solis-Cohen,   M.  D.,  and  A.   A.  Eshner,  M.  D. 

Second  edition,  thoroughly  revised. 

18.  Essentials    of    Practice    of    Phairmacy.     By  Lucius    E.    Sayre.     Second   edition, 

revised  and   enlarged. 

19.  Essentials  of  Diseases  of  the  Nose  and  Throat.     By  E.  B.  Gleason,  M.  D.     Third 

edition,  revised  and  enlarged. 

20.  Essentials  of  Bacteriology.     By  M.  V.  Ball,  M.  D.     Fourth  edition,  revised. 

21.  Essentials  of  Nervous  Diseases  and  Insanity.     By  John  C.  Shaw,  M.  D.     Third 

editicjn,  revist-d. 

22.  Essentials  of    Medical    Physics.      By  Fred  J.   Brockway,  M.  D.     Second  edition, 

revised. 

23.  Essentials  of  Medical  Electricity.     By  David  D.  Stewart,  M.  D.,  and  Edward 

S.  Lawrance,  AL  D. 

24-    Essentials  of  Diseases  of  the  Em.     By   E.  B.   Gleason,   M.  D.     Second   edition, 
revised  and  greatly  enlarged. 

25.    Essentials  of  Histology.     By  Louis  Lkroy,  M.  D.     With  73  original  illustrations. 


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IS 


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Atlas  and  Epitome  of  Internal  Medicine  and  Clinical 
Diagnosis. 

By  Dr.  Chr.  Jakob,  of  Erlangen.  Edited  by  Augustus  A.  Eshner, 
M.  D.,  Professor  of  Clinical  Medicine,  Philadelphia  Polyclinic.  With 
179  colored  figures  on  68  plates,  64  text-illustrations,  259  pages  of  text. 
Cloth,  ^3.00  net. 

Atlas  of  Legal  Medicine. 

By  Dr.  E.  R.  von  Hofmann,  of  Vienna.  Edited  by  Frederick 
Peterson,  M.  D.,  Chief  of  Clinic,  Nervous  Department,  College  of 
Physicians  and  Surgeons,  New  York.  With  120  colored  figures  on  56 
plates  and  193  beautiful  half-tone  illustrations.     Cloth,  $3.50  net. 

Atlas  and  Epitome  of  Diseases  of  the  Larynx. 

By  Dr.  L.  Grunwald,  of  Munich.  Edited  by  Charles  P.  Grayson,. 
M.  D.,  Physician-in-Charge,  Throat  and  Nose  Department,  Hospital  of 
the  University  of  Pennsylvania.  With  107  colored  figures  on  44  plates,^ 
25  text-illustrations,  and  103  pages  of  text.     Cloth,  $2.50  net. 

Atlas  and  Epitome  of  Operative  Surgery. 

By  Dr.  O.  Zuckerkandl,  of  Vienna.  Edited  by  J.  Chalmers 
DaCosta,  M.  D.  ,  Professor  of  Principles  of  Surgery  and  Clinical  Sur- 
gery, Jefferson  Medical  College,  Philadelphia.  With  24  colored  plates, 
217  text-illustrations,  and  395  pages  of  text.      Cloth,  S3. 00  net. 

Atlas   and   Epitome   of    Syphilis    and   the   Venereal 
Diseases. 

By  Prof.  Dr.  Franz  Mracek,  of  Vienna.  Edited  by  L.  Bolton 
Bangs,  M.  D.,  Professor  of  Genito-Urinary  Surgery,  University  and 
Bellevue  Hospital  Medical  College,  New  York.  With  71  colored 
plates,  16  illustrations,  and  122  pages  of  text.     Cloth,  $3.50  net. 

Atlas  and  Epitome  of  External  Diseases  of  the  Eye. 

By  Dr.  O.  Haab,  of  Zurich.  Edited  by  G.  E.  de  Schweinitz,  M.  D., 
Professor  of  Ophthalmolog}^  Jefferson  Medical  College,  Philadelphia. 
With  76  colored  illustrations  on  40  plates  and  228  pages  of  text. 
Cloth,  $3.00  net. 

Atlas  and  Epitome  of  Skin  Diseases. 

By  Prof.  Dr.  Franz  Mracek,  of  Vienna.  Edited  by  Henry  W.  Stel- 
WAGON,  M.  D.,  Clinical  Professor  of  Dermatology,  Jefferson  Medical 
College,  Philadelphia.  With  63  colored  plates,  39  half-tone  illustra- 
tions, and  200  pages  of  text.     Cloth,  S3. 50  net. 

Atlas  and  Epitome  of  Special  Pathological  Histolog(y. 

By  Dk.  H.  Durck,  of  Munich.  Edited  by  Luiavig  Hektoen  M.  D., 
Professor  of  Pathology,  Rush  Medical  College,  Chicago.  In  Two  Parts. 
Part  I.  Ready,  including  Circulatory,  Respiratory,  and  Gastro-intestinaL 
Tract,  120  colored  figures  on  62  plates,  158  pages  of  text.  Part  11. 
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16 


Saunders'  Medical   Hand-Atlases. 


VOLUMES   JUST   ISSUED. 

Atlas  and  Epitome  of  Diseases  Caused  by  Accidents. 

Hy  Dr.  Ed.  (ioLEBiEWSKi,  of  Berlin.  Translated  and  edited  with  addi- 
tions by  Pearce  Bailey,  M.  D.,  Attending  Physician  to  the  Department 
of  Corrections  and  to  the  Almshouse  and  Incurable  Hospitals,  New 
York.  With  40  colored  plates,  143  text-illustrations,  and  600  pages 
of  text.     Cloth,  $4.00  net. 

Atlas  and  Epitome  of  Gynecology. 

By  Dr.  O.  Shaeffer,  of  Heidelberg.  From  the  Second  Revised  Ger- 
man Edition.  Edited  by  Richard  C.  Norris,  A.  M.,  M.  D.,  Gyne- 
cologist to  the  Methodist  Episcopal  and  the  Philadelphia  Hospitals ; 
Surgeon-in-Charge  of  Preston  Retreat,  Philadelphia.  With  90  colored 
plates,  65  text-illustrations,  and  308  pages  of  text.     Cloth,  $3-5°  i^et. 

Atlas   and  Epitome  of  the  Nervous  System  and  its 
Diseases. 

By  Professor  Dr.  Chr.  Jakob,  of  Erlangen.  From  the  Second  Re- 
vised and  Enlarged  German  Edition.  Edited  by  Edward  D.  Fisher, 
M.  D.,  Professor  of  Diseases  of  the  Nervous  System,  University  and 
Bellevue  Hospital  Medical  College,  New  York.  With  ?>^  plates  and  a 
copious  text.     Cloth,  $3.50  net. 

Atlas  and  Epitome  of  Labor  and  Operative  Obstetrics. 

By  Dr.  O.  Schaeffer,  of  Heidelberg.  From  the  Fifth  Revised  and 
Enlarged  German  Edition.  Edited  by  J.  Clifton  Edgar,  M.  D., 
Professor  of  Obstetrics  and  Clinical  Midwifery,  Cornell  University 
Medical  School.      With   126  colored  illustrations.      Cloth,  $2.00  net. 

Atlas    and     Epitome    of     Obstetric     Dia£(nosis     and 
Treatment. 

By  Dr.  O.  Schaeffer,  of  Heidelberg.  From  the  Second  Revised  and  En- 
larged German  Edition.  Edited  by  J.  Clifton  Edgar,  M.  D.,  Professor 
of  Obstetrics  and  Clinical  Midwifery,  Cornell  University  Medical  School. 
72  "colored  plates,  text-illustrations,  and  copious  text.      Cloth,  $3.00  net. 

Atlas   and   Epitome   of   Ophthalmoscopy   and    Oph- 
thalmoscopic   Diagnosis. 

By  Dr.  O.  Haab,  of  Ziirich.  From  the  Third  Revised  and  Enlaj-ged 
German  Edition.  F^dited  by  G.  E.  de  Schweinitz,  M.  D.,  Professor 
of  Ophthalmology,  Jefferson  Medical  College,  Philadelphia.  With  152 
colored  figures  and  82  pages  of  text.      Cloth,  S3-°°  ^let. 

Atlas  and  Epitome  of  Bacteriology. 

Including  a  Text-Book  of  Special  Bacteriologic  Diagnosis.  By  Prof. 
Dr.  K.  B.  Lehmann  and  Dr.  R.  O.  Neumann,  of  Wurzburg.  F?-om  the 
Second  Revised  German.  Edition.  Edited  by  George  H.  Weaver,  M.  D., 
Assistant  Professor  of  Pathology  and  Bacteriology,  Rush  Medical  College, 
Chicago.  Two  volumes  with  o\er  600  colored  lithographic  figures, 
numerous  text-illustrations,  and  500  pages  of  text. 

ADDITIONAL  VOLUMES   IN   PREPARATION. 

17 


NOTHNAGEL'S   ENCYCLOPEDIA 

OF 

PRACTICAL   MEDICINE 

Edited  by  ALFRED   STENGEL.  M.D. 

Professor  of  Clinical  Medicine  in  the  University  of  Pennsylvania ;  Visiting 
Physician  to  the  Pennsylvania  Hospital 

IT  is  universally  acknowledged  that  the  Germans  lead  the  world  in  Internal 
Medicine  ;  and  of  all  the  German  works  on  this  subject,  Nothnagel's  "  Ency- 
clopedia of  Special  Pathology  and  Therapeutics"  is  conceded  by  scholars  to 
be  without  question  the  best  System  of  Medicine  in  existence.  So  necessary 
is  this  book  in  the  study  of  Internal  Medicine  that  it  comes  largely  to  this  country 
.  in  the  original  German.  In  view  of  these  facts,  Messrs.  W.  B.  Saunders  &  Com- 
pany have  arranged  with  the  publishers  to  issue  at  once  an  authorized  edition 
of  this  great  encyclopedia  of  medicine  in  English. 

For  the  present  a  set  of  some  ten  or  twelve  volumes,  representing  the  most 
practical  part  of  this  encyclopedia,  and  selected  with  especial  thought  of  the  needs 
of  the  practical  physician,  will  be  published.  The  volumes  will  contain  the  real 
essence  of  the  entire  work,  and  the  purchaser  will  therefoi'e  obtain  at  less  than 
half  the  cost  the  cream  of  the  original.  Later  the  special  and  more  strictly 
scientific  volumes  will   be   offered  from  time  to  time. 

The  work  will  be  translated  by  men  possessing  thorough  knowledge  of  both 
English  and  German,  and  each  volume  will  be  edited  by  a  prominent  specialist 
on  the  subject  to  which  it  is  devoted.  It  will  thus  be  brought  thoroughly  up  to 
date,  and  the  American  edition  will  be  more  than  a  mere  translation  of  the  Ger- 
man ;  for,  in  addition  to  the  matter  contained  in  the  original,  it  will  represent  the 
very  latest  views  of  the  leading  American  specialists  in  the  various  departments 
of  Internal  Medicine.  The  whole  System  will  be  under  the  editorial  super- 
vision of  Dr.  Alfred  Stengel,  who  will  select  the  subjects  for  the  American  edition, 
and  will  choose  the  editors  of  the  different  volumes. 

Unlike  most  encyclopedias,  the  publication  of  this  work  will  not  be  extended 
over  a  number  of  years,  but  five  or  six  volumes  will  be  issued  during  the  coming 
year,  and  the  remainder  of  the  series  at  the  same  rate.  Moreover,  each  volume 
will  be  revised  to  the  date  of  its  publicatfon  by  the  American  editor.  This  will 
obviate  the  objection  that  has  heretofore  existed  to  systems  published  in  a  number 
of  volumes,  since  the  subscriber  will  receive  the  completed  work  while  the  earlier 
volumes  are  still  fresh. 

The  usual  method  of  publishers,  when  issuing  a  work  of  this  kind,  has  been 
to  compel  physicians  to  take  the  entire  System.  This  seems  to  us  in  many  cases 
to  be  undesirable.  Therefore,  in  purchasing  this  encyclopedia,  physicians  will  be 
given  the  opportunity  of  subscribing  for  the  entire  System  at  one  time ;  but  any 
single  volume  or  any  number  of  volumes  may  be  obtained  by  those  who  do  not 
desire  the  complete  series.  This  latter  method,  while  not  so  profitable  to  the  pub- 
lisher, offers  to  the  purchaser  many  advantages  which  will  be  appreciated  by  those 
who  do  not  care  to  subscribe  for  the  entire  work  at  one  time. 

This  American  edition  of  Nothnagel's  Encyclopedia  will,  without  question, 
form  the  greatest  System  of  Medicine  ever  produced,  and  the  publishers  feel  con- 
fident that  it  will  meet  with  general  favor  in  the  medical  profession. 


NOTHNAGEL^S  ENCYCLOPEDIA 

VOLUMES  JUST  ISSUED  AND  IN  PRESS 


VOLUME  I 
Editor,  William  Osier,  M.D.,  F.R.C.P. 

Professor  of  Medicine  in  Johns  Hopkins 
University 

CONTENTS 
Typhoid  Fever.     By  Dr.  H.  Curschmann, 
of  Leipsic.     Typhus  Fever.     By  Dr.  H. 
CfRSCHMANX,  of  Leipsic. 

Handsome  octavo  volume  of  about  600  pages. 
Just  Issued 


VOLUME  II 

Editor,  Sir  J.  W.  Moore,  B.  A.,  M.D., 
F.R.CP.I.,  of  Dublin 

Professor  of  Practice  cf  Medicine,  Royal  College 
of  Surgeons  in  Ireland 

CONTENTS 

Erysipelas  and  Erysipeloid.  By  Dr.  H.  Lex- 
)iAKTZ,  of  Hamburg.  Cholera  Asiatica  and 
Chokra  Nostras.  By  Dr.  K.  xon  Lieber- 
MEISTER,  of  Tiibingen.  Whoooing  Cough 
and  Hay  Fever.  By  Dr.  G.  Sticker,  of 
Giessen.  Varicella.  By  Dr.  Tii.  von  JUR- 
i^ENSEN,  of  Tiibingen.  Variola  (including 
Vaccination).  Ey  Dr.  H.  Immermann,  of 
Basle. 

Handsome  octavo  volume  of  over  700  pages. 
Jtist  Issued 


VOLUME   VII 
Editor,  John  H.  Musser,  M.  D. 

Professor  of  Clinical  Medicine,  University  of 
Pennsylvania 

CONTENTS 

Diseases  of  the  Bronchi.  By  Dr.  F.  A.  Hi  .ff- 
MAN.N,  of  LeipMC.  Diseases  of  the  Pleura. 
By  Dr.  Rosenbach,  of  Berlin.  Pneumonia. 
Bv  Dr.  E.  Aufrecht,  of  Magdeburc 


VOLUME  VIII 
Editor,  Charles  G.  Stockton,  M.  D. 

Professor  of  Medicine,  University  of  Buffalo 
CONTENTS 

Diseases  of  the  Stomach.    By  Dr.  F.  Riegel, 
of  Giessen. 


VOLUME  IX 
Editor,  Frederick  A.  Packard,  M.  D. 

Physician  to  the  Pennsylvania  Hospital  and  to  the 
Children's  Hospital,  Philadelphia 

CONTENTS 

Diseases  of  the  Liver.   By  Drs.  H.  Quincke 
and  G.  Hoppe-Seyler,  of  Kiel. 


VOLUME  m 
Editor,  "WiUiam  P.  Northrup,  M.  D. 

ProfessoV  of  Pediatrics ,  University  and  Bellevue 
Medical  College 

CONTENTS 

Measles.  By  Dr.  Tit.  von  Jurgensen,  of 
lubingen.  Scarlet  Fever.  By  the  same 
author.     Rotheln.    By  the  same  author. 


VOLUME   X 
Editor,  Reginald  H.  Fitz,  A.M.,  M.  D. 

Hersey  Professor  of  the  Theory  and  Practice 
of  Physic,  Harvard  University 

CONTENTS 

Diseases  of  the  Pancreas.     B>y  Dr.  L.  Oser. 
ot   Vienna.     Diseases  of  the  Suprarenals. 

By  Dr.  E.  Neusser,  of  Vienna. 


VOLUME  VI 
Editor,  Alfred  Stengel,  M.  D. 

Professor  of  Clinical  Medicine,  University  of 
Fennsyliuima 

CONTENTS 

Anemia.  By  Dr.  P.  Ehrlich,  of  Frankfort- 
on-the-Main,  and  Dr.  A.  Lazakus,  of  Char- 
lottenburg.  Chlorosis.  By  Dr.  K.  von 
NooRDEN,  of  Frankfort-on-the-Main.  Dis- 
eases of  the  Spleen  and  Hemorrhagic 
Diathesis.    By  Ijr.  .M.  Littkn,  of  ikrlin. 


VOLUMES  IV,  V,  and  XI 
Editors  announced  later 

Vol.  IV. — Influenza  and  Dengue.  By  Dr.  O. 

LeichtensteRn,  of  Cologne.  MalarialDis- 

eases.    By  Dr.  J-  Mannaberg,  of  Vienna. 
\ol.  \. — Tuberculosis  and  Acute  General 

Miliary  Tuberculosis.    By  Dr.  G.  C'  irnet, 

of  Berlin. 

Vol.    XI. — Diseases   of    the   Intestines   and 
Peritoneum.      By   Dr.    H.    Nothnagel, 

of  Vienna. 


19 


CLASSIFIED   LIST 

OF  THE 

MEDICAL    PUBLICATIONS 


OF 


W.  B.  SAUNDERS  Cf  COMPANY 


ANATOMY,  EMBRYOLOGY, 
HISTOLOGY. 

Bblun,    Davidoff,    and    Huber — A  Text- 
Book  of  Histology 

Clarkson — A  Text-Book  of  Histology 

Haynes — A  Manual  of  Anatomy,    .    . 

Heisler — A  Text-Book  of  Embryology 

Leroy — Essentials  of  Histology,  .    .    . 

Nancrede — Essentials  of  Anatomy,  .  . 

Nancrede — Essentials    of    Anatomy 
Manual  of  Practical  Dissection,  .    . 


nd 


BACTERIOLOGY. 

Ball — Essentials  of  Bacteriology 

Frothingliani — Laljoratory  Guide 

Gorhain — Laboratory  Course  in  Bacteri- 
ology  

Lehmann  and  Neumann — Atlas  of  Bacte- 
riology,    

Levy  and  Klemperer's  Clinical  Bacter- 
ology 

Mallory  and  Wright— Pathological  Tech- 
nique  

McFarland — Pathogenic  Bacteria 

CHARTS,  DIET-LISTS,  ETC. 

Griffltll— Infant's  Weight  Chart 

Hart — Diet  in  Sickness  and  in  Health,  .    . 

Keen — Operation  Blank 

Laine — Temperature  Chart, 

Meigs — Feeding  in  Early  Infancy 

Starr— Diets  for  Infants  and  Children,  .    . 
Thomas— Diet-Lists 


13 


CHEMISTRY  AND  PHYSICS. 

Brockway— Essentials  of  Medical  Physics, 
Wolff — Essentials  of  Medical  Chemistry,  . 

CHILDREN. 
An  American  Text-Book  of  Diseases  of 

Children, 

Griffith— Care  of  the  Baby, 

Griffith— Infant's  Weight  Chart 

Meigs — -Feeding  in  Early  Infancy,  .... 
Powell — Essentials  of  Diseases  of  Children, 
Starr— Diets  for  Infants  and  Children,  .    . 

DIAGNOSIS. 

Cohen  and  Eshner— Essentials  of  Diag- 
nosis  

Corwin — Physical  Diagnosis, 

Vierordt — Medical  Diagnosis 

DICTIONARIES. 
The  American  Illustrated  Medical  Dic- 
tionary  

The  American  Pocket  Medical  Dictionary, 
Morten — Nurses'  Dictionary 


EYE,  EAR,  NOSE,  AND  THROAT. 

An  American  Text-Book  of  Diseases  of 

the  Eye,  Ear,  Nose,  and  Throat i 

De  Schweinitz — Diseases  of  the  Eye,    .    .  6 
Friedrich  and  Curtis— Rhinoiogy,  Laryn- 
gology and  Otology 6 

Gleason — Essentials  of  Diseases  of  the  Ear,  15 

Gleason — Ess.  of  Dis.  of  Nose  and  Throat,  15 

Gradle — Ear,  Nose,  and  Throat, 22 

Griinwald   and    Grayson— Atlas  of  Dis- 
eases of  the  Larynx 16 

Haah  and  De  Schweinitz — Atlas  of  Exter- 
nal Disea-.es  of  the  Eye 16 

Haah  and  De  Schweinitz^ Atlas  of  Oph- 
thalmoscopy,       17 

Jackson — .Manual  of  Diseases  of  the  Eye,  8 

Jackson — Essentials   of   Diseases  of   Eye,  15 

Kyle — Diseases  of  the  Nose  and  Throat,  .  9 

GENITO-URINARY. 

An  American  Text-Book  of  Genito-^Jri- 

nary  and  Skin  Diseases, 2 

Hyde  and  Montgomery — Syphilis  and  the 

Venereal   Diseases 8 

Martin — Essentials     of    Minor     Surgery, 

Bandaging,  and  Venereal  Diseases,  ...  15 
Mracek  and  Bangs — Atlas  of  Syphilis  and 

the  Venereal  Diseases 16 

Saundby — Renal  and  Urinary  Diseases,  .  .  11 
Senn — Genito-Urinary  Tuberculosis,  ...  12 
■yecki — Sexual  Impotence, 14 

GYNECOLOGY. 

American  Text-Book  of  Gynecology, 

Cragin — Essentials  of  Gynecology 15 

Garrigues — Diseases  of  Women,  ....     6 
Long — Syllabus  of  Gynecology,  .    .. 
Penrose — Diseasesof  Women,  .   .    . 
Pryor — Pelvic  Inflammations,  .    .    . 
Sihaeffer  &  Norris — Atlas  of  Gynecology,  17 

HYGIENE. 

Abbott — Hygiene  of  Transmissible  Diseases    3 

Bergey — Principles  of  Hygiene 22 

Pyle — Personal   Hygiene 11 

MATERIA  MEDICA,  PHARMACOL- 
OGY, AND  THERAPEUTICS. 

American  Text-Book  of  Therapeutics,  .  .  i 
Butler — Text-Book    of    Materia    Medica, 

Therapeutics,  and  Pharmacology,    ...  4 

Morris — Ess.  of  M.  M.  and  Therapeutics,  15 

Saunders'  Pocket  Medical  Formulary,  .    .  11 

Sayre — Essentials  of  Pharmacy 15 

Sollmann — Pext- Book  of  Pharmacology,  .  22 

Stevens — Manual   of  Therapeutics,    ...  13 

Stoney — Materia   Medica  for  Nurses,    .    .  13 

Thornton — Prescription-Writing 13 


MEDICAL  PUBLICATIONS  OF  \V.  B.  SAUNDERS  6- 


CO. 


MEDICAL  JUPySPRUDENCE  AND 
TOXICOLOGY. 

Chapman— M  e  d  i  c  u  1  J  urispi  udence  and 
Toxicology 1 c 

Golebiewski  and  Bailey— Atlas  of  Dis- 
eases Caused  by  Accidents 17 

Hofmann  and  Peterson— Atlas  of  Legal 
Medicine j(3 

NERVOUS  AND  MENTAL 
DISEASES,  ETC. 

Brower — Manual  of  Insanity 22 

Chapin — Compendium  of  Insanity,    ...  5 
Cliurcll  andPeterson — Nervous  and  Men- 
tal Diseases c 

Jakob  &  Fisher— Atlas  of  Nervous  System,  17 
Shaw— Essentials  of  Nervous  Diseases  and 

Insanity ic 

NURSING. 
Davis — Obstetric  and  Gvnecologic  Nursing,     6 
Griffith— The  Care  of  the  Baby,  .    .    . 
Hart — Diet  in  Sickness  and  in  Health, 
Meigs — Feeding  in  Early  Infancy,  .    . 
Morten — Nurses'  Dictionary,    .... 
Stoney— Materia  Medica  for  Nurses, 
Stoney — Practical  Points  in  Nursing,  . 
Stoney — Surgical  Technic  for  Nurses, 
Watson — Handbook  for  Nurses,     .    . 


OBSTETRICS. 
An  American  Text-Book  of  Obstetrics, 
Ashton — Essentials  bt  Obstetrics, 
Boisliniere — Obstetric  Accidents 
Borland— Modern  Obstetrics,  . 
Hirst— Te.xt-Book  of  Obstetrics, 
Norris— Syllabus  of  Obstetrics,   . 
Schaeffer'and  Edgar- Atlas  of  Obstetri- 
cal Diagnosis  and  Treatment 17 

PATHOLOGY. 
An  American  Text-Book  of  Pathology,    .     2 
DUrck  and  Hektoen— Atlas  of  Pathologic 

Histology 16 

Kalteyer— Essentials  of  Pathology,   ...    15 
Mallory  and  Wright— Pathological  Tech- 
nique  o 

Senn — Pathology  and  Surgical  Treatment 

of  Tumors 12 

Stengel— Text-Book  of  Pathology,     ...    12 
Warren — Surgical  Pathology  and  Thera- 
peutics,    14 

PHYSIOLOGY. 

An  American  Text-Book  of  Physiology,  2 
Budgett— Essentials  of  Phvsiology,  ...  15 
Raymond— Text-Book  of  Physiology,  .  .  11 
Stewart—  Manual  of  Physiology,    ....    13 

PRACTICE  OF  MEDICINE. 

An  American  Year-Book  of  Medicine  and 

Surgery 3 

Anders — Practice  of    Medicine 4 

Eichhorst— Practice  of  Medicine 6 

LockWOOd — Manual    of    the    Practice    of 

Medicine, 9 

Morris — Ess.  of  Practice  of  Medicine,  .    .    15 
Salinger  and  Kalteyer— Modern   Medi- 
cine  u 

Stevens — Manual  of  Practice  of  Medicine,    i  ^ 


SKIN  AND  VENEREAL. 

An  American  Text-Book  of  Genito- 
urinary and  Skin  Diseases 2 

Hyde  and  Montgomery— Syphilis  and  tlie 
Venereal   Diseases,  .    .    .  ' g 

Martin—  Essentials  of  Minor  Surgery, 
Bandaging,  and  Venereal  Diseases.     .    .'    15 

Mracek  and  Stelwagon— Atlas  of  Diseases 
of  tho  Skm j5 

Stelwagon— Essenti, lis  of  Diseases  of  the 
Skin jr 

SURGERY. 

An  American  Text-Book  of  Surgery,   .    .  2 
An  American  Year-Book  of  Medicine  and 

Surgery ^ 

Beck — Fractures 4 

Beck — Manual  of  Surgical  Asepsis,    ...  4 

Da  Costa — Manual  of  Surgery, 5 

International  Text-Book  of  Surgery,  .    .  8 

Keen — Operation  Blank, 8 

Keen — The    Surgical    Complications   and 

Sequels  of  Typhoid  Fever 8 

Macdonald— Surgical  Diagnosis  and  Treat- 
ment   g 

Martin—  Essentials    of     Minor    Surgery, 

Bandaging,  and  Venereal  Diseases,      .    .  15 

Martin— Essentials  of  Surgery 15 

Moore — Orthopedic  Surgery 10 

Nancrede — Principles  of  Surgery,  ....  10 

Pye — Bandaging  and  Surgical  Dressing,     .  11 

Scudder — Treatment  of  Fractures,     ...  12 

Senn — Genito-Urinary  Tuberculosis,  ...  12 

Senn — Practical  Surgery 12 

Senn — Syllabus  of  Surgery, 12 

Senn — Pathology  and  Surgical  Treatment 

of  Tumors 12 

Warren — Surgical  Pathology  and  Thera- 
peutics   14 

Zuckerkandl  and    Da    Costa — Atlas    of 

Operative  Surgery 16 

URINE  AND  URINARY  DISEASES. 

Ogden — Clinical  Examination  of  the  Urine,    10 
Saundby — Renal  and  Urinary  Diseases,    .    11 
Wolflf —  Handbook     of      Urine-Examina- 
tion,      22 

Wolflf —  Essentials  of  Examination  of 
Urine 15 

MISCELLANEOUS. 

Bastin — Laboratory  Exercises  in  Botany,  .      4 
Golebiewski  and  Bailey— Atlas  of  Dis- 
eases Caused  by  Accidents 17 

Gould  and  Pyle— Anomalies  and  Curiosi- 
ties of  Medicine, 7 

Grafstrom— Massage 7 

Keating — How  to  Examine  for  Life  Insur- 
ance,      s 

Saunders'  Medical  Hand-Atlases,  '  '.  '.  16,17 
Saunders'  Pocket  Medical  Formulary,  .  .  'n 
Saunders'  Question-Compends,  .  .  .  14,15 
Stewart    and    Lawrence— Essentials    of 

Medical  Electricitv le 

Thornton— Dose-Book    and    Manual    of 

Prescription-Writing 13 

Van  Valzah  and  Nisbet— Diseases  of  the 
Stomach jq 


THE  LATEST  BOOKS. 


Bergey's  Principles  of  Hygiene. 

The  Principles  of  Hygiene :  A  Practical  Manual  for  Students, 
Physicians,  and  Health  Officers.  By  D.  H.  Bergev,  A.  M.,  M.  D., 
First  Assistant,  Laboratory  of  Hygiene,  University  of  Pennsyl- 
vania.     Handsome  octavo  volume  of  about  500  pages,  illustrated. 

Brower's  Manual  of  Insanity. 

A  Practical  Manual  of  Insanit}-.  By  Daniel  R.  Brower,  M.  D., 
Professor  of  Nervous  and  Mental  Diseases,  Rush  Medical  College, 
Chicago.      i2mo  volume  of  425  pages,  illustrated. 

Gorham's  Bacteriology. 

'  A  Laboratory  Course  in  Bacteriology.     By  F.  P.  Gorham,  M.  A., 

Assistant  Professor  in  Biology,  Brown  University.  l2mo  volume 
of  about  160  pages,  handsomely  illustrated. 

Gradle  on  the  Nose,  Throat,  and  Ear. 

Diseases  of  the  Nose,  Throat,  and  Ear.  By  Henry  Gradle, 
M.  D.,  Professor  of  Ophthalmology  and  Otology,  Northwestern 
University  Medical  School,  Chicago.  Handsome  octavo  volume 
of  800  pages,  profusely  illustrated. 

Sollmann's  Pharmacology. 

A  Text-Book  of  Pharmacology.  By  Torald  Sollmann,  M.  D., 
Lecturer  on  Pharmacology,  Western  Reserve  University,  Cleve- 
land, Ohio.      Royal  octavo  volume  of  about  700  pages. 

Wolfs  Examination  of   Urine. 

A  Handbook  of  Physiologic  Chemistry  and  Urine  Examination. 
By  Chas.  G.  L.  Wolf,  M.D.,  Instructor  in  Physiologic  Chemistr\'. 
Cornell  University  Medical  College.  i2mo  volume  of  about  160 
pages. 


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